Submitted By Vikas C J

ORGANISATION OF PROTEINS

CONTENTS INTRODUCTION CLASSIFICATION OF PROTEINS STRUCTURAL ORGANISATION OF

PROTEINS CONCLUSION REFERENCE

INTRODUCTION Proteins are polymers of 20 different amino acids

joined by peptide bonds. The proteins we observe in nature have evolved,

through selective pressure, to perform specific functions.

The functional properties of proteins depend upon their three-dimensional structures.

The three-dimensional structure arises because particular sequences of amino acids in polypeptide chains fold to generate, from linear chains, compact domains with specific three-dimensional structures

Proteins are polypeptide chains

Amino acids are joined end-to-end during protein synthesis by the formation of peptide bonds.

carboxyl group of one amino acid condenses with the amino group of the next to eliminate water.

CLASSIFICATION OF AMINO ACIDS BY R GROUP

The amino acids are classified into five main classes based on the properties of

their R groups. These are: Non-polar, Aliphatic R Group Aromatic R Group Polar, Uncharged R Group Positively Charged R Group Negatively Charged R group

There are 20 different types of amino acids.

Nonpolar,aliphatic R groups

Aromatic R groups

Polar,uncharged R groups

Positively charged R groups (Basic)

Negatively charged R groups (Acidic)

STRUCTURAL ORGANIZATION OF PROTEINSThe structural and functional features of proteins and protein

complexesare addressed at four levels of hierarchal organization. These

are:1. Primary structure (1o-Structure)2. Secondary structure (2o-Structure)3. Tertiary structure (3o-Structure)4. Quaternary structure (4o-Structure)

PRIMARY STRUCTURE Primary structure refers to amino acid linear

sequence of polypeptide bonds. The primary structure is held together

by covalent or peptide bond , which are made during the process of protein biosynthesis or translation.

The two ends of the polypeptide chains are referred to as the C-terminal (Carboxyl) and the N-terminal (amino) based on the nature of the free group on each extremity.

Here the chain is connected by disulphide linkage

Eg : insulin

SECONDARY STRUCTURE Localized arrangement of adjacent amino acids formed as the

polypeptide chain folds. it consists of alpha helix and beta pleated sheets

Linus Pauling proposed some essential features of peptide units and polypeptide backbone. They are:

The amide group is rigid and planar as a result of resonance. So rotation about C-N bond is not feasible.

Rotation can take place only about N- Cα and Cα – C bonds. Trans configuration is more stable than cis for R grps at Cα

From these conclusions Pauling postulated 2 ordered structures α helix and β sheet

RAMACHANDRAN PLOT• The angle pairs ф and Ѱ are usually plotted against each other

in a diagram called a Ramachandran plot after the Indian biophysicist G.N. Ramachandran who first made calculations of sterically allowed regions.

• Regions in the Ramachandran plot are named after the conformation that results in a peptide if the corresponding ф and Ѱ angles are repeated in successive amino acids along the chain.

• The major allowed regions are the right-handed α helical cluster in the lower left quadrant; The broad region of extended β strands of both parallel and antiparallel β structures in the upper left quadrant; and the small, sparsely populated left-handed α -helical region in the upper right quadrant.

• Left-handed α helices are usually found in loop regions or in small single-turn a helices.

RAMACHANDRAN PLOT

A Ramachandran plot (also known as Ramachandran diagram or a [φ,ψ] plot), originally developed in 1963 by G. N. Ramachandran

Yellow areas : outer limit

White regions : Sterically disallowed for all amino acids except glycine.

Red regions : allowed regions namely the a-helical and b-sheet conformations.

Yellow areas : outer limit

The alpha (α) helix is an important element of secondary structure Alpha helices in proteins are found when a stretch

of consecutive residues all have ф and Ѱ angle pair approximately -60° and -50°, corresponding to the allowed region in the bottom left quadrant of the Ramachandran plot

The α helix is right-handed The α helix has 3.6 residues per turn and a pitch(the

distance the helix rises along its axis per turn) of 5.4 Å.

The a helices of proteins have an average length of ,12 residues, which corresponds to over three helical turns, and a length of ,18 Å.

the backbone hydrogen bonds are arranged such that the peptide C=O bond of the nth residue points along the helix axis toward the peptide N-H group of the (n+4)th residue.

α Keratin—A Coiled Coil It is the principal component of their

horny outer epidermal layer and its related appendages such as hair, horn, nails, and feathers

The conformation of keratin’s coiled coil is a consequence of its primary structure

the two keratin helices are inclined about 18° relative to one another, resulting in the coiled coil arrangement

The central ,310-residue segment of each polypeptide chain has a 7-residue pseudo repeat, a-b-c-d-e-f-g, with non polar residues predominating at positions a and d

Since an helix has 3.6 residues per turn, keratin’s a and d residues line up along one side of each helix

The hydrophobic strip along one helix associates with the hydrophobic strip on another helix.

Because the 3.5-residue repeat in keratin is slightly smaller than the 3.6 residues per turn of a standard helix.

β Sheets

In β sheets hydrogen bonding occurs between neighboring polypeptide chains rather than within one as in an α helix.

Sheets come in two varieties: The antiparallel β sheet, in which neighboring hydrogen-

bonded polypeptide chains run in opposite directions . The parallel β sheet, in which the hydrogen-bonded

chains extend in the same direction• Successive side chains of a polypeptide chain in

a β sheet extend to opposite sides of the sheet with a two-residue repeat distance of 7.0 Å

Fibroin—A β Sheet Insects and arachnids (spiders)

produce various silks to fabricate structures such as cocoons, webs, nests, and egg stalks

Fibroin consist of series of following residues

(-Gly-Ser-Gly-Ala-Gly-Ala-)n The bsheets stack to form a

microcrystalline array in which layers of contacting Gly side chains from neighboring sheets alternate with layers of contacting Ser and Ala side chains

Super secondary structure - collagen

Its strong, insoluble fibers are the major stress-bearing components of connective tissues such as bone, teeth, cartilage, tendon, and the fibrous matrices of skin and blood vessels

A single collagen molecule consists of three polypeptide chains

Collagen has a distinctive amino acid composition. Nearly one-third of its residues are Gly; another 15 to 30% of its residues are Pro

Tertiary Structure The tertiary structure describes the folding of

secondary structures and pack together in part to bury the hydrophobic side chains, forming a compact molecule with very little empty space in the interior

The interactions hold together are polar interactions between hydrophilic groups and van der Waals interaction between nonpolar groups

Factors influencing tertiary structure include

Hydrophobic/hydrophilic interactions

Hydrogen bonding Disulfide linkages Folding by chaperone proteins

The globin fold is present in myoglobin

The first protein X-ray structure, that of myoglobin, was elucidated in the late 1950s by John Kendrew and co-workers

The major types of secondary structural elements, α helices and pleated sheets, commonly occur in globular proteins

The tertiary structure of myoglobin is that of a typical water soluble globular protein

myoglobin, consist only of α helices spanned by short connecting links that have coil conformations

This protein binds and stores oxygen in muscle. It consists of 153 amino acids, which fold into 8 α-helices of differing lengths

Myoglobin A myoglobin polypeptide is

comprised of 8 separate right handed α-helices, designated A through H, that are connected by short non helical regions.

The interior consists almost entirely of nonpolar residues including leucine, valine, methionine, and phenylalanine

 two histidines are the only polar residues which play an integral role in the binding of heme oxygen

Quaternary structure The quaternary structure of a protein describes the

interactions between different peptide chains that make up the protein

The forces that hold different chains together are the same that hold the tertiary structure together, hydrogen bonding between polar R-groups, ionic bonds between charged R-groups, hydrophobic interactions

between nonpolar R-groups, and disulfide bonds

Allostery in Haemoglobin Allosteric regulation is the regulation of an enzyme or

other protein by binding an effector molecule at the protein's allosteric site.

Haemoglobin is an allosteric protein- binding of oxygen to one of the subunits is affected by its interactions with the other subunits

binding of oxygen to haemoglobin is said to be cooperative degree of saturation of myoglobin is always higher than

haemoglobin Myoglobin therefore has a higher affinity for oxygen than

does haemoglobin

REFERENCE David Hames and Nigel Hooper. Instant

notes on biochemistry. Third edition. David L Nelson and Michael M Cox.

Lehninger principles of biochemistry. Fourth edition.

U Sathyanarayana. U Chakrapani. Biochemistry

Richard A Harvey. Biochemistry. Fifth edition.