Transcript Fundamentals of protein structure

Fundamentals of
Protein Structure
Dr. Saba Abdi
Assistant professor
Depatrment Of Biochemistry
King Saud University
Proteins play key roles in a living system
•
examples of protein functions
•
Transport:
Some proteins transports various
substances, such as oxygen, ions,
and so on.
•
Information transfer:
For example, hormones.
•
Catalysis:
Almost all chemical reactions in a
living cell are catalyzed by protein
enzymes.
•
Physical cell support and shape
(tubulin, actin, collagen)
•
Mechanical movement (flagella,
mitosis, muscles)
Alcohol
dehydrogenase
oxidizes alcohols
to aldehydes or
ketones
Haemoglobin
carries oxygen
Insulin controls
the amount of
sugar in the
blood
Protein classification
Classification based of structure:
1. Globular Proteins:
• Usually water soluble, compact, roughly
spherical
• Hydrophobic interior, hydrophilic surface
• Globular proteins include
enzymes,carrier and regulatory proteins
Protein classification
Classification based of structure:
2. Fibrous Protein:
• Provide mechanical support
• Often assembled into large cables or
threads
• a-Keratins: major components of hair
and nails
• Collagen: major component of tendons,
skin, bones and teeth
Protein classification
Classification based of composition:
1. Simple proteins: albumin, lysozyme
1. Conjugated proteins: haemoglobin,
myoglobin, cytochromes,
immunoglobins.
Properties of proteins
Molecular weights range from 10000-several hundred
thousand
•Generally proteins are soluble in water, except the
membrane proteins which are hydrophobic
•Absorb light in the UV range. Maximum absorption
at 280nm due to aromatic a.a
•Have a specific Isoelectric pH [pI]. Positively
charged below PI, and negatively charged above pI
•Proteins are charged molecules, but the charge
depend on the pH of the buffer.
•Move under an electric field and can be separated
by electrophoresis
•Give color reactions; e.g blue color with Ninhydrin
Amino acid: Basic unit of
protein
R
NH3
+
C
Amino group
H
Different side chains,
R, determin the
COO properties of 20
Carboxylic
acid group amino acids.
An amino acid
20 Amino acids
Glycine (G)
Alanine (A)
Valine (V)
Isoleucine (I)
Leucine (L)
Proline (P)
Methionine (M)
Phenylalanine (F)
Tryptophan (W)
Asparagine (N)
Glutamine (Q)
Serine (S)
Threonine (T)
Tyrosine (Y)
Cysteine (C)
Lysine (K)
Arginine (R)
Histidine (H)
Asparatic acid (D) Glutamic acid (E)
White: Hydrophobic, Green: Hydrophilic, Red: Acidic, Blue: Basic
zwitterions
• Under normal cellular conditions amino
acids are zwitterions (dipolar ions):
Amino group =
Carboxyl group =
-NH3+
-COO-
Proteins are linear polymers of
amino acids
R1
R2
NH3＋ C COO ＋ NH3＋ C COO ＋
ー
ー
H
H
A carboxylic acid
H 2O
condenses with an amino
group with the release of a
water
H 2O
R1
R2
R3
NH3＋ C CO NH C CO NH C CO
H
A
F
Peptide
bond
G
N
S
Peptide
bond
H
T
D
K
G
H
S
A
The amino acid
sequence is called as
primary structure
Peptide bond
• Peptide bond - linkage between amino
acids is a secondary amide bond
• Formed by condensation of the a-
carboxyl of one amino acid with the aamino of another amino acid (loss of
H2O molecule)
• Primary structure - linear sequence of
amino acids in a polypeptide or protein
Planar peptide groups in a
polypeptide chain
• Rotation around C-N bond is restricted
due to the double-bond nature of the
resonance hybrid form
• Peptide groups (blue planes) are
therefore planar
Trans and cis conformations
of a peptide group
Nearly all peptide groups in proteins are
in the trans conformation
Amino acid sequence is encoded
by DNA base sequence in a gene
DNA
molecule
＝
・
G
C
G
C
T
T
A
A
G
C
G
C
・
・ DNA base
C
G sequence
C
G
A
A
T
T
C
G
C
G
・
Each Protein has a unique
structure
Amino acid sequence
NLKTEWPELVGKSVEE
AKKVILQDKPEAQIIVL
PVGTIVTMEYRIDRVR
LFVDKLDNIAEVPRVG
Folding!
Hierarchical nature of protein
structure
Primary structure (Amino acid sequence)
↓
Secondary structure （α-helix, β-sheet）
↓
Tertiary structure （Three-dimensional structure
formed by assembly of secondary structures）
↓
Quaternary structure （Structure formed by more
than one polypeptide chains）
Basic structural units of proteins:
Secondary structure
α-helix
β-sheet
Secondary structures, α-helix
and β-sheet, have regular
hydrogen-bonding patterns.
α-helix
α-helix:(is composed of one polypeptide
chain)
•It is spiral structure;
•consisting of a tightly packed, coiled
polypeptide backbone core with the side
chains of the component amino acids
extending outward from the central axis
in order to avoid interfering sterically
with each other.
α-helix
•Right handed α-helix is stabilized by intra-chain
hydrogen bond.
•Counting from the N-terminal end, the C=O group of
each amino acid residue is hydrogen bonded to the N-H
group of the amino acid four residues away from it in
the covalently bonded sequence.
•(each C ) of one a.a. is hydrogen bonded to the (-NH)
of the next fourth amino acid in the chain (1 →4).
•There are 3.6 residuesfor each turn of the helix.
•The pitch (complete turn distance) is 0.54 nm (5.4 A0).
The a-helix
Examples of α-helix
Some proteins are entirely α-helix eg αkeratin fibrous protein in hair.
•Other proteins have different amount
of α-helix e.g. hemoglobin has 80% αhelix
•Some proteins have no α-helices eg β–
keratin in silk
β-pleated sheet
The surface of β-sheet appear pleated and these
structures are called β-pleated sheet
•β-sheet are composed of two or more separate peptide
chains. (β-strands) or segments of polypeptide chains
that are almost fully extended.
•The peptide backbone is almost completely extended.
•It is stabilized by:
•Interchain hydrogen bonds(between the
polypeptide backbone of separate polypeptide
chains)(It is formed between (-NH) group of one chain
or one segment and (C=O) of the adjacent chain (or
segment)
•Intrachain hydrogen bonds(between the
polypeptide backbone of single polypeptide chain
folding back on itself)
•There are two types of β-pleated sheet:•Parallel βsheet •Antiparallel β-sheet
β-pleated sheet
Three-dimensional structure of
proteins
Tertiary
structure
Quaternary structure
TertairyStructure
•It is spatial arrangement of amino acids that are far
apart in the linear sequence.
•The polypeptide chain is folded in three of
dimension. Bonds responsible for its stability:
(1)Hydrogen bonds (between side chains)
(2)Hydrophobic bonds (between the non-polar side
chain of a.a.)
(3)Electrostatic bonds (salt bonds)(Formed between
oppositely charged group in the side chains of amino
acids)e.g. epsilon-amino group of lysine and carboxyl
group of aspartate, interact electrostatically to
stabilize the protein structure.
Quarternary Structure
•This structure for proteins that have more than one
polypeptide chains.
• Refers to the organization of subunits in a protein with
multiple subunits (an “oligomer”)
• Subunits (may be identical or different) have a defined
stoichiometry and arrangement
• Subunits are held together by many weak, noncovalent
interactions (hydrophobic, electrostatic)
•The interaction between subunits are stabilized by:
•hydrogen bonds
•electrostatic bonds
•hydrophobic bonds
e.g. of proteins having quaternary structure:•Insulin (2
subunits), Lactate dehydrogenase enzyme: (4 subunits),
hemoglobin (4 subunits)
Close relationship between
protein structure and its function
Example of enzyme reaction
substrates
enzyme
A
enzyme
B
Matching
the shape
to A
enzyme
A
Binding to A
Digestion
of A!
Hormone receptor
Antibody