Transcript PROTEIN SECONDARY STRUCTURE

Secondary Protein Structure
What to Know
You will only be tested on what is discussed in class
Pay particular attention to topics that are stressed or mentioned several times
Most important are the general principles, not details that require memorization
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Know the classes of secondary structure
– Types of helices and how amide plane influences secondary structure of helices
– Types of pleated sheets
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main differences between the structure of an α-helix and a β-pleated sheet
What is the main cause of sterically forbidden regions of ф and Ψ ?
What type bonds stabilize secondary structures?
How do you use the helical wheel?
What influences stability of different helices and the different types of βpleated sheets?
PROTEIN SECONDARY STRUCTURE
• Relatively short-range in globular proteins.
• Usually long-range in fibrous proteins.
• All ф bond angles are equal and all Ψ
bond angles are equal providing a
repetitive (periodic) structure.
• Stability attained through H-bonds.
Main Classes of Secondary Structure
All these are local structures that are stabilized
by hydrogen bonds
• Alpha helix
• Beta sheet (composed of "beta strands")
• Tight turns (beta turns or beta bends)
What Are the Elements of Secondary Structure in
Proteins, and How Are They Formed?
The amide or peptide bond planes are
joined by the tetrahedral bonds of the αcarbon.
The rotation parameters are φ and ψ.
The conformations shown corresponds
to φ= 180° and ψ= 180°.
One can specify a polypeptide’s
backbone conformation by the torsion
angles (rotation angles) about the Ca-N
bond (f) and Ca-C bond (y) of each of
its amino acid residues
Consequences of the Amide Plane
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Two degrees of freedom per residue for the peptide
chain
• Angle about the Cα-N bond is denoted φ (phi)
• Angle about the Cα-C bond is denoted ψ (psi)
• The entire path of the peptide backbone is known if all φ
and ψ angles are specified
• Some values of φ and ψ are more likely than others.
Many of the possible conformations about an α-carbon between
two peptide planes are forbidden because of steric crowding.
Several noteworthy examples are shown here.
Protein Structure
• Sterically forbidden conformations are those in
which any nonbonding interatomic distance is
less than its corresponding van der Waals
distance
• G. N. Ramachandran was the first to
demonstrate the convenience of plotting phi,psi
combinations from known protein structures
• The sterically-favorable combinations are the
basis for preferred secondary structures
Steric Constraints on φ & ψ
Ramachandran diagram showing the
sterically reasonable values of the angles
φ & ψ.
Shaded regions indicate particularly
favorable values of these angles.
Dots in purple indicate actual angles
measured for 1000 residues (excluding
glycine, for which a wider range of angles
is permitted) in eight proteins.
Hydrogen Bonds in Proteins
A hydrogen bond between a a
backbone C=O and a backbone N-H
in an acetylcholine binding protein
of a snail, Lymnaea stagnalis.
Schematic drawing of a hydrogen
bond between a backbone C=O
and a backbone N-H.
Protein Structure
 Helical Structures
 if a polypeptide chain is twisted by the same
amount about each of its Ca atoms, it assumes a
helical conformation
 helix characterization
 n=number of peptide units per helical turn
 pitch=distance helix rises along axis/turn
 helixes have chirality
Protein Structure
 Helical Structures
 If a particular helix is to be more than transient,
it must be stabilized (H-bonds)
 Only one helical polypeptide conformation has
simultaneously allowed conformation angles and
a favorable hydrogen binding pattern: a=helix, a
particularly rigid arrangement of the polypeptide
chain. Designation: 3.613 p=5.4Å
The α-Helix
Four different representations of the α-helix
First proposed by Linus Pauling and Robert Corey in 1951
A ubiquitous component of proteins, stabilized by H bonds
Protein Structure
 Other Helical Structures
 310 helix: p=6.0Å
frequently occurs as a single turn transition
between the end of an a-helix and the next
portion of the polypeptide chain
 p helix (4.416 helix): p=5.2Å
comparatively wide and flat conformation
results in axial hole too small to admit H2O
yet too wide to allow van der Waals
associations across the helix axis
Exposed N-H and C=O groups at the ends of an
α-Helix can be “capped”.
Four N-H groups at the N-terminal end of an αhelix and four C=O groups at the C-terminal end
lack partners for H-bond formation.
An amphiphilic helix
in flavodoxin:
A nonpolar helix in
citrate synthase:
A polar helix
in calmodulin:
The Beta-Pleated Sheet
• Formed through by side-by-side alignment of
polypeptide strands
• Strands may be parallel or antiparallel
• Stability arises via H-bond interactions
• Distance: 3.5Ao for antiparallel strands
3.3Ao for parallel strands
• Each strand of a beta sheet may be pictured as a
helix with two residues per turn
An antiparallel β-pleated sheet. R groups project alternately above and below the plane of the
sheet. Sheet structure is derived from the tetrahedral placement of substituents on the α
carbon atoms. This is the more stable form of a β-sheet.
Arrangement of hydrogen bonds
in (a) parallel and (b) antiparallel
-pleated sheets.
Parallel sheets: Large;
hydrophobic on both sides of
sheet; interior of globular proteins.
Antiparallel sheets: 2-3 strands;
amphipathic allowing good
boundaries with aqueous
surroundings.
Protein Structure
 Beta structure
 -pleated sheets in globular proteins
typically exhibit a right-handed twist when
viewed along their polypeptide strand
 twists serve important role since  sheets often
form central core of proteins
 in globular proteins,  sheets are common
 parallel  sheets of less than 5 strands are rare,
suggesting they are less stable than antiparallel
sheets (H-bonds are distorted for parallel sheets)
Protein Structure
 Beta structures
 mixed parallel-antiparallel sheets are
common but occur less frequently than
expected from random mixing of
strands
The Beta Turn
• allows the peptide chain to reverse direction
• carbonyl C of one residue is H-bonded to the
amide proton of a residue three residues away
• proline and glycine are prevalent in beta turns
The structures of two kinds of -turns (also called tight turns or -bends).
Proline and glycine are frequently situated in positions 2 and 3, respectively.
Protein Structure
 Beta structures
 links between 2 antiparallel
sheets=hairpin turn
 links between 2 parallel sheets=crossover connection
Fibrous Proteins
• Much or most of the polypeptide chain is
organized approximately parallel to a single axis
• Fibrous proteins are often mechanically strong
• Fibrous proteins are usually insoluble
• Usually play a structural role in nature
Alpha Keratin
• Found in hair, fingernails, claws, horns and
beaks
• Sequence consists of 311-314 residue alpha
helical rod segments capped with non-helical
N- and C-termini
• Primary structure of helical rods consists of 7residue repeats: (a-b-c-d-e-f-g)n where a and
d are nonpolar. Promotes association of
helices!
(a) Both type I and type II a-keratin molecules have sequences consisting of long,
central rod domains with terminal cap domains. Asterisks denote domains of
variable length.
(b) (b) The rod domains form coiled coils consisting of intertwined right-handed ahelices. These coiled coils then wind around each other in a left-handed twist.
Keratin filaments = twisted protofibrils (each a bundle of four coiled coils)
Beta Keratin
• Found in silk fibers
• Alternating sequence:
Gly-Ala/Ser-Gly-Ala/Ser....
• Since residues of a beta sheet extend alternately above
and below the plane of the sheet, this places all
glycines on one side and all alanines and serines on
other side!
• This allows Glys on one sheet to mesh with Glys on an
adjacent sheet (same for Ala/Sers)
Silk fibroin consists of a unique stacked array of b-sheets. The primary
structure of fibroin molecules consists of long stretches of alternating glycine
and alanine or serine residues.
When the sheets stack, the more bulky alanine and serine residues on one
side of a sheet interdigitate with similar residues on an adjoining sheet.
Glycine hydrogens on the alternating faces interdigitate in a similar manner,
but with a smaller intersheet spacing.