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Hierarchical Structure of Proteins

Proteins are the polymers L--aminoacids. The structure of proteins is rather

complex which can be divided into 4 levels oforganization (Fig.4.4).

Overview

1. Primary structure : The linearsequence of amino acids forming thebackbone of proteins (polypeptides)

2. Secondary structure : The spatialarrangement of protein by twisting of

the polypeptide chain. Twoarrangements that are particularlystable are called the -helix and the-pleated sheet.

3. Tertiary structure : The threedimensional structure of a functionalprotein. It is a final, stable, foldedstructure, including supersecondarymotifs.

4. Quaternary structure : Some of theproteins are composed of two ormore polypeptide chains referred toas subunits. The spatial arrangementof these subunits is known as

quaternary structure.

Primary structure

1. The primary structure is the linearsequence of amino acids composing apolypeptide.

2. Peptide bond is the covalent amidelinkage that joins amino acids in aprotein.

3. The primary structure of a proteindetermines its secondary (e.g., -helices and -sheets) and tertiarystructures (overall three-dimensionalstructure).

4. Mutations that alter the primarystructure of a protein often change its

function and may change its charge,as in the following example.

a. The sickle cellmutation alters the primarystructure and the charge bychanging glutamate to valine.

Specific folding of primarystructure determines the finalnative conformation.

b. This alters themigration of sickle cellhemoglobin onelectrophoresis.

Secondary structure

1. Secondary structure is the regulararrangement of portions of apolypeptide chain stabilized byhydrogen bonds.

2. The -helix is a spiral conformation ofthe polypeptide backbone with theside chains directed outward.

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a. Proline disrupts the -helixbecause its -imino group hasno free hydrogen tocontribute to the stabilizinghydrogen bonds.

Proline: helix breaker

3. The -sheet consists of laterallypacked -strands, which are extendedregions of the polypeptide chain.

The -sheets are resistant toproteolytic digestion.

4. Motifs are combinations of secondarystructures occurring in differentproteins that have a characteristicthree-dimensional shape.

a. Supersecondary structures

often function in the bindingof small ligands and ions or inprotein-DNA interactions.

Leucine zippers and zincfingers: supersecondarystructures commonly found inDNA-binding proteins

b. The zinc finger is asupersecondary structure inwhich Zn2+ is bound to 2cysteine and 2 histidine

residues. (1) Zinc fingers are

commonly found inreceptors that have aDNA-binding domainthat interacts withlipid-solublehormones (e.g.,cortisol).

c. The leucine zipper is asupersecondary structure inwhich the leucine residues ofone -helix interdigitate withthose of another -helix tohold the proteins together ina dimer.

(1) Leucine zippersare commonly foundin DNA-bindingproteins (e.g.,transcription factors).

5. Prions are infectious proteins formedfrom otherwise normal neuralproteins through an induced changein their secondary structure.

Prions: infectious proteins formed bychange in secondary structureinstead of genetic mutation;responsible for kuru and Creutzfeldt-Jacob disease

a. Responsible forencephalopathies such askuru and Creutzfeldt-Jacobdisease in humans

b. Induce secondary structurechange in the normal form oncontact

c. Structural change frompredominantly -helix innormal proteins topredominantly -structure inprions

d. Forms filamentousaggregates that are resistantto degradation by digestion orheat

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