Transcript No Slide Title

Secondary structure - local folding of the backbone of a linear
polymer to form a regular, repeating structure. For a polypeptide,
the secondary structure is determined by the amino acid sequence
and the solvent environment in which it is located.
The sequence of amino acids dictates geometric constraints for
the polypeptide. These include maximum lengths between
covalent bonds, limiting angles in which bonds can be bent, and
van der Waals radii, which limit how tightly structures can be
packed. These factors, along with forces that help preferentially
stabilize structures, such as H- bonds, ionic attractions/ repulsions,
hydrophobic interactions, and others, ultimately determine the
shape that a peptide has over a short distance. The structure
resulting from all these interactions is the secondary structure of
the protein.
1
Secondary structure should not be confused with
the overall shape of a polypeptide. The overall
shape of a polypeptide arises from the different
regions of secondary structure folding upon each
other and is called the tertiary structure if it
involves only the same peptide or the quaternary
structure if it involves two or more separate
peptides.
2
Important points:Partial double bond
character of the peptide bond. Caused by
localization of the pi-orbitals over O-C-N.
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Alpha-Helix
The alpha-helix and beta-sheet are common protein
secondary structures that were originally predicted
by Linus Pauling.
The alpha-helix structure repeats after exactly 18
residues, which amounts to 5 turns. It has,
therefore, 3.6 residues per turn. Since the pitch of a
helix is given by p = nh, we have for the helix, with
a rise of 0.15 nm/residue, p = 3.6 (res/turn) x 0.15
(nm/res) = 0.54 nm/turn. Parameters for the other
helices shown in Figure 6.3 and Figure 6.4 are listed
in Table 6.1.
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In an alpha-helix each carbonyl oxygen is H-bonded to the
amide proton on the fourth residue up the helix. Thus, if
one includes the H-bond, a loop of 13 atoms is formed.
Each of the helices shown in Figure 6.3 and Figure 6.4 has
a different number of atoms in such a hydrogen-bonded
loop. We shall call this number N. A quick way to describe
a polypeptide helix, then, is by the shorthand nN, where n
is the number of residues per turn. The 310 helix fits this
description; it has exactly 3.0 residues per turn and a 10member loop. The alpha-helix could also be called a 3.613
helix.
5
The alpha-helix
repeats after 18
residues, which is 5
turns-therefore 3.6
residues /turn. The
pitch of a helix = nh
and h= 1.5  /residue
= 5.4 /turn of helix.
Idealized helices
The pitch (p) of the helix is the distance parallel to the axis in
which the helix makes one turn. There may be an integral number
of residues/turn or not.
The rise of the helix is the distance parallel to the axis from the
level of one residue to the next.
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The Beta-Pleated Sheet
This is the second famous structure. It is best
envisioned by laying thin, pleated strips of paper side
by side to make a pleated sheet. Each strip of paper can
be envisioned as a single peptide strand in which the
peptide backbone makes a zigzag pattern along the
strip, with the alpha-carbons lying at the folds of the
pleats. This structure can exist in both parallel and
antiparallel forms. In the parallel form, adjacent chains
run in the same direction- either N-to-C or C-to-N . In
the antiparallel form, adjacent strands run in opposite
directions.
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Each single strand of sheet can be looked at
as a helix with two residues/turn. The Hbonds in this structure are interstrand rather
than intrastrand.
H-bonds formed in the parallel sheet are
bent substantially. The side chains in the
pleated sheet are oriented perpendicular
(normal) to the plane of the sheet, extending
out from the plane on alternating sides.
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Parallel sheets have a narrower range of
allowed dihedral angles than antiparallel
sheets. In addition, the parallel sheet
structures that form are typically large >5
strands ; antiparallel structures are smaller.
Antiparallel structures are the fundamental
ones found in silk, with the polypeptide
chains the form the sheets funning parallel
to the silk fibers.
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The beta pleated sheet has
each residue rotated by 180 o
with respect to the preceding
one, which is an n=2 helix.
Chains can have their NC
directions run parallel or
antiparallel.
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Hydrogen bonding in beta sheets
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Note !! The beta strand is an element of secondary
structure, while the beta sheet actually involves
tertiary structure, since it brings together regions
of the molecule, which may be widely separated
in the primary sequence
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The Beta-turn
Since proteins are globular
structures, it is evident that
the chains have to be able to
turn and reorient
themselves.The simple betabend is one in which the
peptide chain forms a tight
loop with the C=O oxygen
of one residue H-bonded
with the amide proton of the
residue three positions down
the chain.
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RAMACHANDRAN PLOTS:
I. THE BACKBONE CONFORMATION IS DESCRIBED BY THE
ANGLES OF ROTATIONS AROUND TWO BONDS:
1.THE BOND BETWEEN THE N-ATOM AND 2. THE alpha-CARBON
(phi) AND THE BOND BETWEEN THE alpha-CARBON AND THE
CARBONYL CARBON (psi).
CONVENTION TO DEFINE THE DIRECTION OF POSITIVE
ROTATION AND THE 0O VALUE:
PRETEND THAT YOU ARE SITTING ON THE alpha-CARBON .
POSITIVE ANGLES OF ROTATION ARE CHOSEN FOR THE
CLOCKWISE DIRECTION NO MATTER WHICH WAY YOU ARE
LOOKING.
A VALUE OF 0O CORRESPONDS TO AN ORIENTATION WITH THE
AMIDE PLANE BISECTING THE H-C alpha-R (SIDE CHAIN) PLANE
AND A CIS CONFIGURATION OF THE MAIN CHAIN AROUND THE
ROTATING BOND IN QUESTION.
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(II) THE BAC KBONE CONFORM ATION OF ANY RESIDUE IS
A POINT IN phi, psi SPACE. THE RAM ACHANDR AN PLOT IS
A PLOT OF THESE TWO ANGLES. CERTAIN REGIONS IN
THE PLOT RESULT IN ATOMS IN THEIR CHAINS
APPRO AC HING CLOSER THAN THEIR VAN DER W AALS
RADII PERMIT. ONLY A FRACTION OF THE CONCEIVABLE
CONFORM ATIONS IS PER MITTED.
(III) FOR PROTEIN WITH REG ULAR SECOND ARY
STRUCT URE ALL RESID UES HAVE EQUIVALENT phi, psi
VALUES AND CAN THEREFORE BE DESCRIBED AS A POINT
ON THE PLOT.
(IV) SIDE CHAIN EFFECTS ARE RE LATIVELY SM ALLBULKIER CHAINS RESULT IN SHRIN KING ALLOWED
REGIONS.
The fraction of area that is totally allowed is 7-8 %; partially
allowed regions due to conformational flexibility is ~ 22.5%
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Rotation around the bonds in a polypeptide chain
Two amide planes are shown; Rotation is allowed around
the N-Calpha and Calpha -C=O bonds. These (phi, psi)
angles have directions defined as positive rotation shown
by the arrows.
The chain conformation shown here corresponds to an extended
structure with both phi and psi = 180 o.
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The C=O oxygen (residue I-1) and the H atom on
residue I+1 overlap. Therefore this pair of angles is
disallowed.
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This comparison is for prediction
of the secondary structure of BPTI
The Chou-Fasman rules are
compared with the secondary
structure deduced from the X-Ray
data. The agreement is good.
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The phenomenon of circular dichroism is very sensitive to the secondary
structure of polypeptides and proteins. Circular dichroism (CD)
spectroscopy is a form of light absorption spectroscopy that measures the
difference in absorbance of right- and left-circularly polarized light
(rather than the commonly used absorbance of isotropic light) by a
substance. It has been shown that CD spectra between 260 and
approximately 180 nm can be analyzed for the different secondary
structural types: alpha helix, parallel and antiparallel beta sheet, turn, and
other. In fact, optical rotary dispersion (ORD) data suggested a righthanded helical conformation as a major protein structural element before
the Pauling and Corey model and Kendrew's structure of myoglobin.
Modern secondary structure determination by CD are reported to achieve
accuracies of 0.97 for helices, 0.75 for beta sheet, 0.50 for turns, and
0.89 for other structure types
In proteins the aromatic bond structures are of importance in
spectroscopy. For protein structure studies we are primarily
concerned with backbone conformations. The peptide bond
amide group is the dominant chromophore of the polypeptide
backbone and has a weak absorption maxima at 220nm and a
stronger absorption maxima at 195nm. Circular dichroism
makes use of the fact that right and left handed polarized light
are absorbed slightly differently in asymmetric molecules.
Even though individual amide groups in protein backbones
have a symmetric transition dipole, their mutual interaction in
highly oriented secondary structures induces asymmetries
which translated into circular dichroism spectra (difference of
absorption of left and right handed polarized light not zero).
Protein secondary structure can be revealed based on their
characteristic electronic circular dichroism behavior between
190 and 220nm.
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Circular dichroism to study secondary structures of proteins
Amino acids are optically active molecules and in a polypeptide are often found as
part of regular secondary structures. The frequent occurrence of alpha helices and
beta sheets in proteins has thus been exploited by measuring the presence of such
regularly arranged units from circular dichroism spectra of protein solutions.
Although CD measurements are not useful to obtain high resolution structures, but
merely secondary structure content of a protein, this information is useful to study
the status of protein folds. It can generally be assumed that the absence of any
alpha helical or beta strand components indicate the unfolded state of a protein.
Dichroism occurs when light absorption differs for different direction of polarized
light. Light can be polarized either in a linear way, where the plane of the electric
vector is fixed while its amplitude oscillates, or in a circular way, where the plane
of polarization of the electric vector is modulated while the amplitude remains
constant. The electric vector of circularly polarized light describes a helix which
may be right-handed or left-handed.
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Circular Dichroism spectra of poly-L-lysine in the alpha-helical, beta-sheet and
random coil conformations as indicated. Similar spectra may be obtained
for other polyamino acids, so they reflect backbone secondary structures, primarily.
Spectra of proteins may be analyzed to determine the amount of these three
conformations that are present.
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Cartoon drawings of: A) triosephosphate isomerase (H:0.52, S:0.14, T:0.11, O:0.23);
B) hen egg lysozyme (H:0.36, S:0.09, T:0.32, O:0.23); C) myoglobin (H:0.78, S:0.0,
T:0.12, O:0.10); and D) chymotrypsin (H:0.10, S:0.34, T:0.20, O:0.36). Secondary
structures are color coded red:helix. green:strand, and yellow:other.
FT-infrared spectroscopy
Like circular dichroism analyses of proteins, Fourier transform infrared (FT-IR)
spectroscopic studies and are easily performed and require relatively small
amounts of material (~0.1 mg). The infrared spectra of polypeptides exhibit a
number of so-called amide bands which represent different vibrational modes of
the peptide bond. Of these, the amide I band is most widely used for secondary
structure analyses. The amide I band results from the C=O stretching vibration of
the amide group. These vibrational modes, present as infrared bands between
approximately 1600-1700 cm-1, are sensitive to hydrogen bonding and coupling
between transition dipole of adjacent peptide bonds and hence are sensitive to
secondary structure.
A critical step in the interpretation of IR spectra of proteins is the assignment of
the amide I component bands of different types of secondary structure. Amide I
bands centered around 1650-1658 cm-1 are generally considered to be
characteristic of alpha helices. Unordered structure and turns also give rise to
amide I bands in this region complicating analyses. Beta sheets give rise to highly
diagnostic bands in the region 1620-1640 cm-1. Parallel and antiparallel beta
strands are distinguishable only as antiparallel strands contain a large splitting of
the amide I band due to the interstrand interactions. Water (H2O) also has an
intense IR band in the region of the amide I band and requires that samples are
measured in 2H2O or that the solvent resonance is subtracted (digitally).
The IR spectrum of peptides and proteins is fairly
sensitive to secondary structure. IR spectra acquired
with polarized radiation provide information about
the orientation of the absorbing groups.
The vibrational modes of the peptide bond shown
above are:
Secondary structure sensitivity:
-1
N-H stretch ~3300 cm
alpha helix 1650
beta sheet doublet 1620(s), 1690 (w)
C=O stretch ~ 1650 cm-1
Mixed C-N stretch and N-H in-plane bend ~ 1550 cm-1
The C=O stretch of the side chain appears at 1734 cm-1
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Secondary structure from FT-IR spectra
Numerous attempts have been made to extract quantitative information on protein secondary
structure from analyses of these amide I bands (for reviews see Byler & Susi, 1986;Surewicz,
et al, 1993). Both curve-fitting and pattern recognition techniques have been applied with
varying success. Since the potential sources of error in CD and FT-IR analyses of secondary
structure content are largely independent, the two methods are highly complementary and
could be used in conjunction to increase accuracies. Despite limitations in the quantitative
assessment of protein secondary structure content, FT-IR (like CD) provides a good tool to
monitor conformational changes in polypeptides and proteins
NMR spectroscopy
In the past 20 years, nuclear magnetic resonance (NMR) spectroscopy has
proved itself as a potentially powerful alternative to X-ray crystallography for
the determination of macromolecular three-dimensional structure. NMR has
the advantage over crystallographic techniques in that experiments are
performed in aqueous solution as opposed to a crystal lattice. However, the
physical principles that make NMR possible, limit the application of this
technique to macromolecules of less than 35-40 kD. Fortunately, a large
number of globular proteins and most protein domains fall into this molecular
weight regime.
It is possible to determine the secondary structure of a protein using NMR
techniques without determining the three-dimensional structure. Of the three
most commonly used methods of secondary structure determination not
requiring a three-dimensional structure, NMR is potentially the most powerful.
Unlike secondary structure determinations by CD and IR which provide
overall secondary structure content (% helix, % sheet, etc.), using NMR
parameters, secondary structures are localized to specific segments of the
polypeptide chain. However, obtaining secondary structure from NMR data
requires considerably more material (milligrams) and effort (requires
sequence specific resonance assignments) than the other spectroscopic
techniques and is limited to proteins of molecular weight amenable to NMR
investigation (<35-40 kD).
Sub-atomic particles (e.g., proton, neutron, electron, etc.) possess a
characteristic called spin angular momentum. From quantum mechanics,
each particle has a spin value of 1/2. The combination of multiple particles in
the nucleus results in an overall spin property for each atomic isotope. Those
isotopes with an even number of protons and neutrons will have zero
magnetic spin (e.g., He-4, C-12 and O-16). An odd number of protons and an
even number of neutrons (e.g., H-1, N-15, or F-19) or an odd number of
neutrons and an even number of protons (e.g., He-3, O-17 or Ca-41) result in
an overall (multiple of 1/2) spin. Those isotopes with odd numbers of both
protons and neutrons (e.g., H-2 or N-14) have more complex spin states and
are less suitable for direct NMR observation in macromolecules. Fortunately,
each of the four most abundant elements in biological material (H, C, N, and
O) have at least one naturally occurring isotope with non-zero nuclear spin
and is in principle observable in an NMR experiment. The naturally occurring
isotope of hydrogen, H-1, is present at >99% abundance and forms the basis
of the experiments described here. Other important NMR-active isotopes
include C-13 and N-15 present at 1.1 and 0.4% natural abundance,
respectively. The low natural abundance of these two isotopes makes their
observation difficult on commonly isolated natural products. These two nuclei
are however very extensively used for larger (>10 kD) proteins which can be
isotopically enriched (to >95% if necessary) when cloned into over expression
systems.
In the presence of an external magnetic field, the spin angular momentum of
nuclei with isotopes of overall non-zero spin will undergo a cone-shaped
rotation motion called precession. The rate (frequency) of precession for each
isotope is dependent on the strength of the external field and is unique for
each isotope. For example, in a magnetic field of a given strength (e.g. 14.1
Tesla) all protons in a molecule will have characteristic resonance
frequencies (chemical shifts) within a dozen or so parts per million (ppm) of a
constant value (e.g., 600.13 MHz) characteristic of the particular nuclear type.
These slight differences are due to the type of atom the proton is bound (e.g.,
C, N, O, or S) and the local chemical environment. Thus each proton should,
in principle, be characterized by a unique chemical shift. In practice, this is
never observed as some protons such as the three protons of each sidechain
methyl group of Thr, Val, Leu, Ile, and Met and most pairs of equivalent (2,6
and 3,5) aromatic ring protons are found to have degenerate chemical shifts.
Other protons (e.g., some OH, SH, and NH3) are in rapid chemical exchange
with the solvent and thus have chemical shifts indistinguishable from the
solvent resonance. Nevertheless, nearly complete chemical shift assignments
are often possible and are a prerequisite for structural studies by NMR.
Structural information from NMR experiments come primarily from
through-bond (scalar or J coupling) or through space (the nuclear
Overhauser effect NOE) magnetization transfer between pairs of protons.
J couplings between pairs of protons separated by three or fewer covalent
bonds can be measured. The value of a three-bond J coupling constant
contains information about the intervening torsion angle. This is called
the Karplus relationship and has the form:
3J = A cos (theta) +B cos2 (theta) + C
where A, B, and C are empirically derived constants for each type of
coupling constant Unfortunately in general, torsion angles cannot be
unambiguously determined from a Karplus-type relationship since as
many as four different torsion angle values correlate with a single
coupling constant value as seen below. Similar relationships can be
determined between the three-bond coupling constant between the alpha
proton and the beta proton(s) yielding information on the value of the
sidechain dihedral angle chi1. Constraints on the dihedral angles phi and
chi1 are important structural parameters in the determination of protein
three-dimensional structures by NMR.
The other major source of structural information comes from through space dipole-dipole
coupling between two protons called the NOE. The intensity of a NOE is proportional to the
inverse of the sixth power of the distance separating the two protons and is usually observed
if two protons are separated by < 5 Angstroms. Thus the NOE is a sensitive probe of short
intramolecular distances. NOEs are categorized according to the location of the two protons
involved in the interaction. Intraresidual NOEs are between protons within the same residue
whereas sequential, medium, and long range NOEs are between protons on residues
sequentially adjacent, separated by 1, 2 or 3 residues, and separated by four or more
residues in the polypeptide sequence. A network of these short inter-proton distances form
the backbone of three-dimensional structure determination by NMR.
Hydrophobic residues sequester inside of
globular proteins-a result of the hydrophobic
effect Horse Heart Cytochrome C
Red = hydrophobic residues, Green = Hydrophilic residues
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Collagen:
- Rigid, inextensible fibrous protein
-principal constituent of connective tissue
(tendons, cartilage, bones, teeth, skin and blood vessels).
- basic structural unit is tropocollagen
(three intertwined polypeptide chains of ~1000 amino acids,
molecular weight of 285,000)
-tropocollagen is 300 nm long and 1.4 nm in diameter.
-Primary structure: high gly (1/3 of the amino acids) and pro.
-uncommon amino acids are also found in the structure, 3- and 4hydroxyproline, and 5-hydroxylysine (G and G 174).
-higher order of structure. Staggered arrays of tropocollagen form
organized fibrils giving rise to a characteristic banded pattern in
EM studies.
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α-KERATIN
-d o minated b y alpha- helical segments of polypept ide
-a mino ac id seq uence is a central alpha- helical rich do ma in of 311- 314
res id ues flanked by no n-he lical – and C-ter minals of vary ing size and
co mpos itio n.
-typ ical structure: 4 he lical strands ara nged as twisted pairs of two
strand ed coiled co ils.
-p rimary structure is a q uasi-rep eating 7 resid ue segments of the fo rm
(ab cdefg )n . These units are not true repeats b ut a and d are usua lly nonpo lar amino ac ids which must be, and are bur ied in the rope like
structure
-In so me forms of kerat in, S-S bo nds form between cyste ine res id ues of
ad jac ent mo lecu les, making the structure inso lub le.
-o ccurs in c laws, fingernails, ha ir and horns.
The S-S bo nds may be red uced and clea ved in ha ir-then reo xid ized and
re-for med to change the curl or wave (“p erma nent”).
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Type structures of globular proteinsNotation devised by Jane Richardson
Blue spirals-alpha helices
Orange segments beta sheets
Arrow heads at the end of beta strands
point in the N  C direction
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Regions of secondary structure are themselves folded
into specific compact structures of the whole polyypeptide
chain. Each atom occupies a specific position. This is
known as tertiary structure.
N.B. Each copy of a native protein molecule has approximately
the same three dimensional structure as all other copies.
This is not the case for synthetic polymers where there is
usually a statistical distribution of conformations present
in solution.
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Helical Wheel Plots
To construct a helical wheel plot, a
projection of the residues in a helix is
made along the helical axis onto the XY plane. In an alpha helix, the helix
repeats every 3.6 residues. Thus, each
residue is 100o from its neighbor.
Example:
The myoglobin E Helix sequence:
SEDLKKHGATVLTALGGIL
The helical wheel plot shows that the
hydrophobic residues are concentrated
along one side of the helix. This is the
side of the helix that faces the
hydrophobic core of the protein
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Ribbon diagram of the bovine pancreatic trypsin inhibitor
backbone and the three disulfide bonds.
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Diagram of the hydrogen bonds between polypeptide
backbone atoms of BPTI.
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Zinc ion
Carbonic anhydrase polypeptide chain. The C-terminal is inserted
through the plane of other segments of the polypeptide chain. A
a knot would result if it were pulled downward. The white ball in
the middle is a Zn2+ bound to the protein through the imidazole side
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chains of three His residues.
The four internal water molecules of BPTI are marked
( orange arrow ) pointing to their O atoms.
The water molecules pair with internal polar
groups in the protein
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Generic energy level diagram for electronic spectroscopycalled a Jablonski diagram. S= singlet states (paired electrons;
T= triplet states (unpaired electrons)
Absorption within the ground electron state constitutes the
IR process. Raman scattering is not shown.
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Energy Transfer as a Spectroscopic ruler
Energy Transfer-Schematic of Processes
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Energy Transfer-Equations !!!!!
Efficiency of transfer =
ro6/ (ro6 + r6 )
Where r = distance between donor and acceptor
ro = characteristic distance for the donor acceptor pair that
depends on spectroscopic parameters of the donor and accptor
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Classes of Protein Structures:
1. alpha-mostly alpha-helical (4 helix bundles)
2. beta-mostly beta- sheet (barrels)
3. Alpha,beta-repeating alternating helix and
sheets
4. alpha+beta- segregated helix and sheets.
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Beta-alpha-beta motifs
Antiparallel beta-strands can be linked by short lengths of
polypeptide forming beta-hairpin structures. In contrast, parallel
beta-strands are connected by longer regions of chain which cross
the beta-sheet and frequently contain alpha-helical segments. This
motif is called the beta-alpha-beta motif and is found in most
proteins that have a parallel beta-sheet. The loop regions linking the
strands to the helical segments can vary greatly in length. The helix
axis is roughly parallel with the beta-strands and all three elements
of secondary structure interact forming a hydrophobic core. In
certain proteins the loop linking the carboxy terminal end of the first
beta-strand to the amino terminal end of the helix is involved in
binding of ligands or substrates. The beta-alpha-beta motif almost
always has a right-handed fold as demonstrated in the figure.
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Simplest way to pack helices: antiparallel
manner, with a slight left-handed twist of
the helix bundle. Mostly these occur as fourhelix bundles. Example is tobacco
mosaic virus protein.
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The leucine zipper arises from the periodic
repetition of Leu side chains from the same side
of the helical cylinder, where they can enter into
hydrophobic interactions with a similar set of Leu
side chains extending from a matching
helix in a second polypeptide. The motif appears
in protein dimerization.
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Helix-turn-helix
The loop regions connecting alpha-helical segments can have
important functions. For example, in parvalbumin there is helix-turnhelix motif which appears three times in the structure. Two of these
motifs are involved in binding calcium by virtue of carboxyl side
chains and main chain carbonyl groups. This motif has been called the
EF hand as one is located between the E and F helices of parvalbumin.
It now appears to be a ubiquitous calcium binding motif present in
several other calcium-sensing proteins such as calmodulin and
troponin C.
EF hands are made up from a loop of around 12 residues which has
polar and hydrophobic amino acids at conserved positions. These are
crucial for ligating the metal ion and forming a stable hydrophobic
core. Glycine is invariant at the sixth position in the loop for structural
reasons. The calcium ion is octahedrally coordinated by carboxyl side
chains, main chain groups and bound solvent.
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Postranslational Modifications:
1. Deacylation, acylation of N-terminus
2. Proteolysis
3. Methylation
4. Phosphorylation
5. Sidechain modification for cross-linking
6. Conversion of sidechains to prosthetic groups
7. Attachment of prosthetic groups
8. Attachment of lipids
9. glycosylation
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Symmetry:
-Proteins with globular subunits are usually
arranged with a high degree of symmetry
-near-symmetry or absence of symmetry may
suggest a regulatory role
-fibrous proteins are less symmetrical and are
composed of less symmetrical subunits.
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LAST LEVEL OF PROTEIN STRUCTURE: QUATERNARY
SUBUNITS - SPECIFIC AGGREGATES OF TWO OR MORE
POLYPEPTIDE CHAINS.
INTERACTIONS BETWEEN FOLDED POLYPEPTIDE CHAINS IN
MULTISUBUNIT PROTEINS ARE ALL OF THE SAME WEAK
INTERACTIONS WE HAVE DISCUSSED PREVIOUSLY.
INTERACTIONS BETWEEN IDENTICAL SUBUNITS RESULT IN
SOME TYPE OF SYMMETRIC STRUCTURE.
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THE LANGUAGE USED TO DESCRIBE THE SYMMETRY OF
THESE STRUCTURES - GROUP THEORY- THE PARTICULAR
SYMMETRY ARRANGEMENT IS CALLED THE POINT GROUP.
PARTICULAR POINT GROUPS ARE DEFINED BY THEIR
COLLECTION OF SYMMETRY ELEMENTS.
(1) AXIS OF SYMMETRY- An N-FOLD AXIS OF SYMMETRY IS
PRESENT IN THE SYSTEM IF A ROTATION OF THE
STRUCTURE BY 360/N DEGREES PRODUCES A STRUCTURE
INDISTINGUISHABLE FROM THE ORIGINAL.
3 FOLD AXIS = ROTATION BY 120 0 .
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Quaternary Structure of collagen
-Assembly of triple helices into microfibrils
-Interactions between triple helices produce arrays of parallel
molecules with a stagger of 234 residues (674 )
-After assembly, the structure is stabilized by a wide variety
of covalent cross-links between the triple helices n involving
primarily the hydroxy-lysine side chains.
In bone-collagen provides a matrix that is cemented in a rigid
structure by deposits of crystals in a poorly crystalline phase
of hydroxyapatite:
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(Ca)10(PO4)10(OH)2
DIMERS - MOST COMMON FORM OF INTERACTION.
OFTEN DIMERS HAVE FURTHER INTERACTIONS
AND GIVE RISE TO STRUCTURES OF HIGHER
SYMMETRY. THE OCCURRENCE OF THREE
MUTUALLY PERPENDICULAR TWO FOLD AXES
IS COMMON. THIS CORRESPONDS TO THE D2
POINT GROUP.
MOLECULES EXHIBITING THIS TYPE
OF SYMMETRY HAVE A WELL-DEFINED (SMALL)
NUMBER OF SUBUNITS
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SO METIMES >1 TYPE OF POLYPEPTIDE CHAIN IS INVOLVED
IN INTER ACTIO NS TO PRODUCE SYMMETRY. HEMOG LOBIN
IS MADE UP OF TWO TYPES OF CHAINS, alpha AND beta. THE
INT ACT STR UCTURE CONSISTS OF TWO OF EACH CHAIN,
AND IS REFERRED TO AS AN alpha2 beta2 DIMER. THE MOST
IMPORTANT CO NTACTS IN THE STRUCTURE ARE BETWEEN
alpha AND beta, RATHER THAN alpha,alpha OR beta, beta.
IT TURNS OUT THAT THESE INTERACTIO NS BETWEEN
SUBUNITS CONTROL THE PROTEIN FUNCTION.
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Subunit-subunit interactions
-the hydrophobic effect
-H bonding (sheets)
-helix stacking
-salt bridges
-S-S bond-metal ions
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