The amino acids in their natural habitat

The amino acids in their natural habitat

Topics:

• Hydrogen bonds• Secondary Structure

• Alpha helix• Beta strands & beta sheets• Turns• Loop

• Tertiary & Quarternary Structure• Protein Domains

Hydrogen Bonds

 A hydrogen bond is a type of attractive (dipole-dipole) interaction between an electronegative atom and a hydrogen atom bonded to another electronegative atom.

Hydrogen Bond Donors (D):

Nitrogen e.g. N-H amide in peptide bondOxygen e.g. O-H sidechain of Ser

Hydrogen Bond Acceptors (A):

Oxygen e.g. C=O carbonyl in peptide bond

Distance: H-A 2.5 Å; D-A 3.5 Å; also dependent on angle D-H … A

Hydrogen Bonds (2)

Secondary structure

The amino acids form four different secondary structure elements:α-helicesβ-strandsTurnsLoops

Secondary structure: the -helix

• hydrogen bond between backbone O (from C=O) of residue i and backbone H (from N-H) of residue i+4:

O(i) – N(i+4)

• 3.6 residues per turn • right-handed helix

The -helix

Helix

Helix dipole• All peptide unit planes are roughly parallel to the helix axis• Each peptide bond is a small dipole• The dipoles within the helix are aligned, i.e. all C=O groups point in the same

direction and all N-H groups point the other way• The helix becomes a net dipole with +0.5 charge units at the N-terminal and –

0.5 at the C-terminal• By convention the dipole points from negative to positive

Helix summary

Hydrophobicity distributionHydrogen bond between O(i) and N(i+4)

Helix dipole

Secondary structure – β-strand

A β-sheet consists of at least two β-strands interact with each other

Anti-parallel Parallel

-strands and -sheets

• Backbone adopts an “extended” conformation: -strand

• The -strands are arranged side by side; adjacent -strands can be parallel or anti-parallel

Backbone hydrogen bonding between adjacent -strands; formation of a -sheet

• R-groups extend below and above the sheet, perpendicular to the plane of the H-bonds

• The strand is twisted

Residue direction in -sheets

R-groups of neighbouring residues within one -strand point in opposite directions. R-groups of neighbouring residues on adjacent -strands point in the same direction

Antiparallel -sheet

N -> C

C <- N

Parallel -sheet

N -> C

N -> C

Bulge

An irregularity in antiparallel structures

Hydrogen-bonding of two residues from one strand with one residue from the other in antiparallel sheets

Strand summary

Multiple strands form a sheetHydrophobicity distribution alternatingParallel and anti-parallel strands & hydrogen bonding patternsBulges are irregularities

Secondary structure – Turn

Turns connect the secondary structure elements

Turns

Specialized secondary structures that allow for chain reversal without violating conformational probabilities

Nearly one-third of the amino acids in globular proteins are found in turns.

Most turns occur at the surface of the molecule.

A specific subclass is the -turn, a region of the polypeptide of 4 amino acids (i, i+1, i+2, i+3, between two -strands) having a hydrogen bond from O(i) to N(i+3).

-Hairpin

•Widespread in globular proteins. •One of the simplest super-secondary structures

Turn summary

A turn sits between two ‘things’A -turn sits between two -strandsThere are many types of -turn Nearly all -turns contain at least one Gly or Pro

Secondary structure - Loop

A loop is everything that has no defined secondary structure

Tertiary structure

The secondary structure elements interact to form the structured protein

Quaternary structure

Some proteins can interact with each other to form dimers or multimersThe individual chains are callled subunits or monomers

Protein domains - definitions

• Group of residues with high contact density, number of contacts within domains is higher than the number of contacts between domains.

• A stable unit of protein structure that can fold autonomously

• A rigid body linked to other domains by flexible linkers.

• A portion of the protein that can be active on its own if you remove it from the rest of the protein.

Protein Domains

• Domains can be 25 to 500 amino acids long; most are less than 200 amino acids

• The average protein contains 2 or 3 domains

• The same or similar domains are found in different proteins.“Nature is a ‘tinkerer’ and not an inventor” (Jacob, 1977).“Nature is smart but lazy”

• Usually, each domain plays a specific role in the function of the protein.

Protein Domains - an alphabet of functional modules

WD40 WWSH2 SH3

14-3-3 ANK3 ARM BH1 C1 C2 CARD

EH EVH FYVE PDZDeath DED EFH

PH PTB SAM

From: Bioinformatics.ca

Domain Database InterPro

InterPro - protein sequence analysis & classification

InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites.

Interpro combines protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool

Summary 3D, 4D & domains

Proteins are folded up in 3DProtein subunits can fold up to form a quarternary structureSometimes monomer is not active, but quarternary structure isProtein domains

“independent units” with own function& structureAverage size 100-150 aaLego blocks of natureLook in Interpro to find info about domains in your protein