Unit 3

The Three-Dimensional Structure of Proteins

PROTEIN: Structure and Function
Most abundant biomolecule in
the cell
They adopt a specific three-
dimensional conformation.
Conformation: spatial arrangement of
atoms in a protein
This three-dimensional structure
of a protein is called native
conformation.
Native proteins: proteins in any of their
functional, folded conformation.
Native conformation is essential
for the biological function of a
protein.
Loss of structure results in loss
of biological function Na+-K+ ATPase Pump
PROTEIN: Structure and Function
Types of proteins
Structural for support; Ex. Collagen, elastin
Catalytic for hastening biochemical reactions; Ex. Amylase
Storage for storage of amino acids; Ex. Casein, ovalbumin
Transport for transport of other substances;
Ex. Hemoglobin, protein channels in cellular membranes
Regulation for regulation/coordination of bodily activities;
Ex. Insulin, glucagon
Receptor for response of cell to external stimuli;
Ex. Neuron receptors in nerve cells
Contractile for movement; Ex. Myosin, actin
Defensive for protection against disease; Ex. Antibodies
STRUCTURAL ORGANIZATION OF PROTEIN
Levels of structural organization of proteins
Primary structure
Secondary structure
Tertiary structure
Quaternary structure
PRIMARY STRUCTURE
It refers to the sequence of amino acids in a polypeptide
chain (read from the N- to C-terminal end).
It determines the native conformation of the peptide/protein.
SECONDARY STRUCTURE
It refers to the ordered 3D
arrangements in localized N H O C
regions of a polypeptide
The 1o structure dictates the 2o structure.
chain (regular folding)
H-bonded arrangement
of backbone of the
Spatial arrangement of protein is possible due to
the atoms in the free rotation of bonds
polypeptide chain between:
-C and -N (phi )
-C and carboxyl
Formed and stabilized by carbon (psi )
hydrogen bond between
the amide proton and
carbonyl oxygen
SECONDARY STRUCTURE
Kinds of Secondary Structure
-Helix
-Pleated sheet
-bends or reverse bends
Random coil
Other helical structures
SECONDARY STRUCTURE: -Helix
Spiral structure
Stabilized by intramolecular
hydrogen bonds
Structural features:
C=O of each peptide bond is
hydrogen bonded to the N-H of the
fourth amino acid away; there are
3.6 aa/turn
Pitch: 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)
SECONDARY STRUCTURE: -Helix

Formation of H-bond of n and n+4 amino acid in -helix

Position of R-group relative The -helices found in proteins are

to polypeptide backbone almost always right-handed.
Constraints to Helix Stability

Presence of helix breakers

Pro: (1) the rotation around the N-C bond is restricted bec
it is part of the ring (2) N has no H to participate in H-bonds
Gly: has more conformational flexibility due to its R-group; it
supports other conformations (e.g. coil or bend)

Electrostatic repulsion (or attraction) between successive

charged aa residues.

Bulkiness (steric strain) between adjacent R-groups

However, small hydrophobic residues (e.g. Ala, Leu) are
strong helix formers
SECONDARY STRUCTURE: -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
Structural features:
Each -strand (polypeptide chain in
-sheet) is extended into a zigzag.
H-bonds form 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
Types of -Pleated Sheets

ANTI-PARALLEL -SHEET PARALLEL -SHEET

-strands in an anti-parallel sheet -strands in a parallel sheet run in

run in opposite directions resulting same direction resulting to bent
in linear H-bonds (stronger) H-bonds (weaker)
SECONDARY STRUCTURE: -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.
SECONDARY STRUCTURE: Random Coils

These are nonrepetitive

structures.
An irregular or unique
conformation
SECONDARY STRUCTURE: Other Helices
SUPERSECONDARY STRUCTURES

Combinations of and -strands

Example: unit, unit, -meander and Greek key

Motif: repetitive supersecondary structures

TERTIARY STRUCTURE
It refers to three-dimensional
conformation of the entire
polypeptide.
Stabilized by numerous
interactions between amino acid
side chains.
Covalent bonds (e.g. disulfide
bond between 2 cys)
H-bonds
Salt bridges (electrostatic)
Hydrophobic interaction
Major classes: Fibrous and
globular
TERTIARY STRUCTURE
Fibrous proteins polypeptide chain arranged in long
strands or sheets
Consists largely of one type of 2o structure
Function: structural (strength and support)
Example: collagen, keratin
Most are water insoluble.

Globular proteins polypeptide

chain folded into compact,
spherical structure
Consists of many types of 2o
structure
Function: metabolic (catalytic,
transport, etc.)
Example: enzymes, hemoglobin
They are largely water soluble.
QUATERNARY 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 3o structure).
Dimer, 2 subunits; trimer, 3
subunits; tetramer, 4 subunits;
etc..
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
High temperature
Change in pH
Change in ionic strength
Organic solvents (e.g. urea,
alcohol)
Reducing agents (e.g. performic
acid and mercaptoethanol)
Detergents
Salts of heavy metals