Biochemistry by Campbell and Farrell (8E)

Chapter Four: The Three-Dimensional Structure of Proteins

4.1 The Structure and Function of Proteins

Proteins are the most abundant biomolecules in the cell.
Proteins adopt a three-dimensional conformation (spatial arrangement of atoms).
The 3D structure of a protein with biological function is referred as the native conformation.
Loss of structure results a loss in biologic functions.
4.2 Types of Proteins
a) Structural Proteins e) Regulation Proteins
For support Coordination of bodily activities
Collagen, elastin Insulin; Glucagon
b) Catalytic Proteins f) Receptor Proteins
Hastens biochemical reactions Response of cell to external stimulus
Amylase and pother enzymes Neurons
c) Storage Proteins g) Contractile Proteins
Storage of Amino Acids For movement
Casein, Ovalbumin Myosin; Actin
d) Transport Proteins h) Defensive Proteins
Transport substances Protection against disease
Hemoglobin; Protein Channels Antibodies

4.3 Structural Organization of a Protein

I. Primary Structure of a Protein
The sequencing/arrangement of amino acids in a polypeptide
Determines the native conformation of peptide or protein
II. Secondary Structure
Refers to the ordered 3D arrangements of localized regions of a polypeptide chain (regular folding)
Spatial arrangement of the atoms in a polypeptide chain
Formed and stabilized by hydrogen bond between the amide proton and carbonyl oxygen
a. Alpha-Helix
Spiral structure
Stabilized by intramolecular hydrogen bonds
C=O of each peptide bond is hydrogen bonded to the N-H of the fourth amino acid away
o N + 4 manner
There are 3.6 aa/turn
Pitch is 5.4
H-bonds are parallel to helical axis
All R groups point outward from helix
Coil of the helix either right-handed (clockwise) or left-handed (counter-clockwise)
 o The -helices found in proteins are almost always right-handed.
Helix Stability
i. Helix Breakers
Proline
o Rotation around N-C bond is restricted because it is part of the ring
o N has no H to participate in H-bonds
Glycine
o has more conformational flexibility due to its R-group
o it supports other conformations (e.g. coil or bend)
ii. Electrostatic Repulsion
between successive charged amino acid residues.
iii. Steric Strain
between adjacent R-groups
However, small hydrophobic residues (e.g. Ala, Leu) are strong helix formers
b. Beta-pleated Sheets
It is formed when 2 or more polypeptides line up side by side
Stabilized by hydrogen bonds (intrachain or interchain) of adjacent polypeptide chains
Each -strand (polypeptide chain in -sheet) is extended into a zigzag.
H-bonds formed are adjacent between -strands.
All R groups extend above or below the sheet in an alternating up and down direction.
Adjacent -strands can run in parallel or anti-parallel manner
o -strands in an anti-parallel sheet run in opposite directions resulting in linear H-bonds
(stronger)
o -strands in a parallel sheet run in same direction resulting to bent H-bonds (weaker)
c. Beta-Bends
It permits the change in direction (usually about 180o) of the peptide chain.
It connects -helices and -strands and allow the polypeptide chain to fold back on itself,
producing compact 3D-conformation.
H-bond stabilizes the -bend.
A -bend is accomplished over 4 aa residues.
Gly and Pro are frequently part of the -bends.
d. Random Coils
These are non-repetitive structures.
An irregular or unique conformation.
Supersecondary Structures
Combinations of and -strands
The repetitive supersecondary structures is called as a motif.
i. unit iii. -meander
ii. unit iv. Greek key
 III. Tertiary Structure
It refers to three-dimensional conformation of the entire polypeptide.
Typically, protein achieves native conformation
Stabilized by numerous interactions between amino acid side chains.
Covalent bonds (e.g. disulfide bond between 2 cys)
Non-covalent interactions:
H-bonds
Salt bridges (electrostatic) / Ionic Interactions
Hydrophobic interaction
Major classes
Fibrous Globular
polypeptide chain arranged in long polypeptide chain folded into compact,
strands or sheets spherical structure
Consists largely of one type of 2 Consists of many types of 2 structure
structure Function: metabolic (catalytic,
Function: structural (strength and transport, etc.)
support) Example: enzymes, hemoglobin
Example: collagen, keratin They are largely water soluble.
Most are water insoluble.
IV. Quaternary Structure
Not all proteins assume this structure
It refers to spatial arrangement of polypeptide subunits.
It is formed by the assembly of individual polypeptides (subunit/monomer) into a larger functional
cluster.
Subunits are stabilized by noncovalent interactions (similar to 3 structure).
Dimer, 2 subunits; trimer, 3 subunits; tetramer, 4 subunits; etc
4.4 Denaturation
It refers to a change in the native conformation of the protein that disrupts protein function.
Alteration in the environment disrupting the bonds and forces of interaction that stabilized protein
structure
Affects secondary and tertiary structures
Factors
o High temperature
o Change in pH
o Change in ionic strength
o Organic solvents (e.g. urea, alcohol)
o Reducing agents (e.g. performic acid and mercaptoethanol)
o Detergents
o Salts of heavy metals