Protein structure

Proteins

-Dr Nidhi Sharma

Protein StructureFour levels of organization

•Primary structure•Secondary structure

oAlpha helixoBeta pleated sheets

•Tertiary structure•Quaternary structure

Dr Nidhi Sharma

Protein Structure

Dr Nidhi Sharma

• Proteins are the major components of livingorganisms and perform a wide range ofessential functions in cells.

• While DNA is the information molecule, it isproteins that do the work of all cells -microbial, plant, animal.

• Proteins regulate metabolic activity, catalyzebiochemical reactions and maintain structuralintegrity of cells and organisms.

Dr Nidhi Sharma

Proteins can be classified in a variety of ways, including their biological function

Type: Example:

Enzymes- Catalyze biological

reactionsß-galactosidase

Transport and Storage Hemoglobin

MovementActin

And Myosin in muscles

Immune ProtectionImmunoglobulins

(antibodies)

Regulatory Function within

cellsTranscription Factors

HormonesInsulin

Estrogen

Structural Collagen

Dr Nidhi Sharma

Proteins can be formed using 20 different building blockscalled amino acids.

Each of these amino acid building blocks has a differentchemical structure and different properties.

Each protein has a unique amino acid sequence that isgenetically determined by the order of nucleotide basesin the DNA, the genetic code.

Since each protein has different numbers and kinds ofthe twenty available amino acids, each protein has aunique chemical composition and structure

Dr Nidhi Sharma

A change in just one amino acid can change thestructure and function of a protein.

For example, sickle cell anemia is a disease thatresults from an altered structure of the proteinhemoglobin, resulting from a change of the sixthamino acid from glutamic acid to valine. (This is theresult of a single base pair change at the DNA level.)

This single amino acid change is enough to changethe conformation of hemoglobin so that this proteinclumps at lower oxygen concentrations and causesthe characteristic sickle shaped red blood cells of thedisease.

Dr Nidhi Sharma

Amino acid structure:Amino acids are composed of carbon, hydrogen,

oxygen, and nitrogen.

Two amino acids, cysteine and methionine, alsocontain sulfur.

All amino acids have an amino group (NH2) and acarboxyl group (COOH) bonded to the same carbonatom, known as the alpha carbon.

Dr Nidhi Sharma

Dr Nidhi Sharma

Amino acids differ in the side chain or R group that isbonded to the alpha carbon. Glycine, the simplestamino acid has a single hydrogen atom as its R group- Alanine has a methyl (-CH3) group.

The chemical composition of the unique R groups isresponsible for the important characteristics ofamino acids such as chemical reactivity, ionic chargeand relative hydrophobicity.

Dr Nidhi Sharma

The amino acids are grouped according to theirpolarity and charge.

They are divided into four categories, those withpolar uncharged R groups, those with apolar(nonpolar) R groups, acidic (charged) and basic(charged) groups.

Dr Nidhi Sharma

Dr Nidhi Sharma

The polar amino acids are soluble in water becausetheir R groups can form hydrogen bonds with water.

For example, serine, threonine and tyrosine all havehydroxyl groups (OH).

Dr Nidhi Sharma

The acidic amino acids carry a net negative charge at neutral pH contain a second carboxyl group.

These are aspartic acid and glutamic acid, also called aspartate and glutamate, respectively.

Dr Nidhi Sharma

The basic amino acids have R groups with a net positive charge at pH 7.0.

These include lysine, arginine and histidine.

Dr Nidhi Sharma

There are eight amino acids with nonpolar Rgroups. As a group, these amino acids are lesssoluble in water than the polar amino acids.

These are alanine, valine, leucine, isoleucine,tryptophan, phenylalanine, methionine, andproline

If a protein has a greater percentage of nonpolar Rgroups, the protein will be more hydrophobic(water hating) in character.

Dr Nidhi Sharma

A protein is formed by amino acid subunits linkedtogether in a chain.

The bond between two amino acids is formed by theremoval of a H20 molecule from two different aminoacids, forming a dipeptide.

The bond between two amino acids is called apeptide bond and the chain of amino acids is called apeptide (20 amino acids or smaller) or a polypeptide.

Dr Nidhi Sharma

IH

Dr Nidhi Sharma

Primary Structure refers to the linear sequence ofamino acids that make up the polypeptide chain.

This sequence is determined by the genetic code, thesequence of nucleotide bases in the DNA.

The sequence of amino acids determines thepositioning of the different R groups relative to eachother.

This positioning therefore determines the way that theprotein folds and the final structure of the molecule.

Dr Nidhi Sharma

Fig. A pentapeptide. The chain starts at the

amino acid end

Dr Nidhi Sharma

The secondary structure of protein molecules refers tothe formation of a regular pattern of twists or kinks ofthe polypeptide chain.

The regularity is due to hydrogen bonds formingbetween the atoms of the amino acid backbone of thepolypeptide chain.

The two most common types of secondary structureare called the alpha helix and ß pleated sheet.

Dr Nidhi Sharma

Fig. Right handed α helix

Dr Nidhi Sharma

Fig. Antiparallel β pleated sheet

Dr Nidhi Sharma

Tertiary structure refers to the three dimensionalglobular structure formed by bending and twisting ofthe polypeptide chain.

This process often means that the linear sequence ofamino acids is folded into a compact globular structure.

Dr Nidhi Sharma

The folding of the polypeptide chain is stabilized bymultiple weak, noncovalent interactions. Theseinteractions include:

Hydrogen bonds that form when a Hydrogen atomis shared by two other atoms.

Electrostatic interactions that occur betweencharged amino acid side chains. Electrostaticinteractions are attractions between positive andnegative sites on macromolecules.

Dr Nidhi Sharma

Hydrophobic interactions: During folding of thepolypeptide chain, amino acids with a polar (watersoluble) side chain are often found on the surface ofthe molecule while amino acids with non polar(water insoluble) side chain are buried in theinterior. This means that the folded protein issoluble in water or aqueous solutions.

Covalent bonds may also contribute to tertiarystructure.

The amino acid, cysteine, has an SH group as part ofits R group and therefore, the disulfide bond (S-S ) canform with an adjacent cysteine. For example, insulinhas two polypeptide chains that are joined by twodisulfide bonds.

Dr Nidhi Sharma

Quaternary structure refers to the fact that some proteinscontain more than one polypeptide chain, adding anadditional level of structural organization: the association ofthe polypeptide chains.

Each polypeptide chain in the protein is called a subunit.

The subunits can be the same polypeptide chain or differentones. For example, the enzyme ß-galactosidase is a tetramer,meaning that it is composed of four subunits, and, in thiscase, the subunits are identical - each polypeptide chain hasthe same sequence of amino acids.

Dr Nidhi Sharma

Hemoglobin, the oxygen carrying protein in theblood, is also a tetramer but it is composed oftwo polypeptide chains of one type (141 aminoacids) and two of a different type (146 aminoacids).

In chemical shorthand, hemoglobin is referred toas a2ß2 .

For some proteins, quaternary structure isrequired for full activity (function) of the protein.

Dr Nidhi Sharma

Fig. Four levels of organization of protein structure

Dr Nidhi Sharma

Dr Nidhi Sharma