chapter 3. protein structure and function. proteins are the most versatile macromolecules in living...

Chapter 3. Protein structure and function

Proteins

are the most versatile macromolecules in living systems.

serve crucial functions in essentially all biological processes.

functions as catalysts.

Several key properties of proteins

1.Proteins are linear polymers built of monomer units called amino acids.

2.Proteins contained a wide range of functional groups. (alcohols, thiols, thioesters, carboxylic acids, basic groups)

3. Proteins can interact with one another and with other biological macormolecues to form complex assembles.

4. Some proteins are quite rigid, whereas others display limited flexibility.

- Only L amino acids are found in proteins.

Proteins are built from a repertoire of 20 amino acids

The L and D isomers of amino acids.

Ionization state as a function of pH

Peptide bonds are quite stable kinetically because the rate of hydrolysis is extremely slow

Primary structure: amino acids are linked by Peptide bonds to from polypeptides chains

Amino acid sequences have direction

Main chain or backbone: H bond donor-NH, H bond acceptor-CO,

Side chain: dependent on residues

The mean molecular weight of amino acid residue is ~110 g/mol (Da)

Components of polypeptide chain

Disulfide bond: Cross-links

Disulfide bond: Cross-links

Amino acid sequence of bovine insulin

Intra-molecule disulfide bond Inter-molecule disulfide bond

Proteins have unique amino acid sequences

knowing a.a. sequences is important for several reasons.

Knowledge of AA sequence 1. is essential to elucidating its mechanism of action.2. determine the 3D structures of proteins3. is a component of molecular pathology4. reveal much about its evolutionary history

Peptide bond is planar

Polypeptide chains are flexible yet conformationally restricted.

Peptide bond has considerable double-bond character, which prevents rotation about this bond

Almost all peptide bonds in proteins are trans

Steric clashes between groups attached to the alpha-carbon hinder formation of the cis form

Trans and cis X-pro bonds.The energies of these froms are realtively balaced because stric clashes occur in both forms

Most common cis peptides are X-proline linakges

In contrast with peptide bonds, the bonds btwn the amino group and the a-carbon atom and btwn the a-carbon and C-group are single bond.

This freedom of rotation about two bonds of each amino acid allows proteins to fold in many different ways.

By convention, both φand ψare defined as 0 when the twopeptide bonds flanking that carbon are in the same plane and positioned as shown.

The conformations of peptides are defined by the values of φand ψ. Conformations deemed possible are those that involve little or no steric interference, based on calculations using known van der Waals radii and bond angles.

Secondary Structure: Spatial arrangement of amino acid residues

Polypeptide chains can fold into regular structures such as the alpha helixbeta sheet, and turns and loops.

Alpha Helix

Structure of -helix

The CO group of each amino acid forms a hydrogen bond with the NH group of the amino acid that is situated four residues ahead in the sequence.

Q) Why does the α helix form more readily than many other possible conformations?

A) in part, an α helix makes optimal use of internal hydrogen bonds.

H-bond scheme for an -helix

Right handed Helices: 손가락 기준으로 시계반대방향Left handed Helices: 손가락 기준으로 시계방향

Five different kinds of constraints affect the stability of an α helix

(1)the electrostatic repulsion (or attraction) between successive amino acid residues with charged R groups

(2) the bulkiness of adjacent R groups

(3) the interactions between R groups spaced three (or four) residues apart

(4) the occurrence of Pro and Gly residues

(5) the interaction between amino acid residues at the ends of the helical segment and the electric dipole inherent to the α helix.

β-sheets

A β-strand is almost fully extended rather than being tightly coiled as in the α helix.

Structure of a β-strand

Anti-parallel arrangement

Parallel arrangement

Simple H-bonds

Complicated H-bonds

Polypeptide chains can change direction by making reverse turns or loops

Reverse turn = -turn = hairpin bend

Loops = omega Loops

Beta-Turn: connect the ends of two adjacent segmentsof an antiparallel β sheet

Structure of a reverse turnH-bond: CO of i and NH of i+3

Loops: no structural characteristics, more elaborate structurea responsible for chain reversal

Loops on a protein surface

Surface loops that mediate interactions with other molecules

Antibody

Tertiary structure: Protein ArchitectureThe overall three-dimensional arrangement of all atoms in a protein

Fibrous proteins, having polypeptide chains arranged in long strands or sheetsex: alpha-keratin

Globular proteins, having polypeptide chains folded into a spherical or globular shapeex: myoglobin

Myoglobin: the first protein to be seen in atomic level

Three dimensional structure of myoglobin

Quaternary structure:

Spatial arrangement of subunits and the nature of their interactions

The teramer structure of human hemoglobin

The amino acid sequence of a protein determines its three dimensional structure

1. Amino acids have different properties for forming -helix, sheets and turns

2. Protein folding is highly cooperative process.

3. Proteins fold by progressive stabilization of intermediates rather than random search

4. Prediction of three D structure from sequence remains a great challenge.

5. Protein modification and cleavage confer new capabilities