©CMBI 2001

The amino acids in their natural habitat

©CMBI 2001

The amino acids in their natural habitat

Topics:

HydrophobicityHydrogen bonds steer secondary structure

Hydrogen bonds in the helixHelix dipoleHydrogen bonds in strands

Parallel versus anti-parallel strandsTurnsIrregularitiesFolds and structural hierarchy

©CMBI 2002

Hydrogen Bonds

Two electronegative atoms compete for the same hydrogen 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

©CMBI 2002

Hydrogen Bonds (2)

Geometry of Hydrogen Bond D-H …. A:

Distance

H-A 2.5 ÅD-A 3.5 Å

Angle

The ideal hydrogen bond would have an angle of 180° between the lone-pair of the acceptor atom, the polar hydrogen and the donor atom

©CMBI 2002

The -helix

• hydrogen bond between backbone carbonyl O(i) and hydrogen of N(i+4)• 3.6 residues per turn • right-handed helix

©CMBI 2002

The -helix

©CMBI 2002

Helix

©CMBI 2002

Helix dipole

All peptide units point in the same direction (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

©CMBI 2002

Helix dipole

©CMBI 2002

Helix summary

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

Helix dipole

©CMBI 2002

-strands and -sheets

Backbone adopts an “extended” conformation

Hydrogen bonding between main chain C=O and N-H groups of two or more adjacent -strands forms a -sheet

Adjacent strands can be parallel or anti-parallel

R-groups extend perpendicular to the plane of the H-bonds.

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

The strand is twisted

©CMBI 2002

Residue direction in -sheets

©CMBI 2002

Antiparallel -sheet

N -> C

C <- N

©CMBI 2002

Parallel -sheet

N -> C

N -> C

©CMBI 2002

Mixed -sheet

©CMBI 2002

Bulge

An irregularity in antiparallel structures

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

©CMBI 2002

Strand summary

Multiple strands form a sheetHydrophobicity distribution alternatingParallel and anti-parallelHydrogen bond patternsBulges are irregularities

©CMBI 2002

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.

©CMBI 2002

Turns

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

-turns can be classified into several subclasses based on the and angles of residues i+1 and i+2.

Most common turn types: Type I and Type II.

©CMBI 2002

-Turns, Type I & I’

©CMBI 2002

-Hairpin

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

©CMBI 2002

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

©CMBI 2002

Classes of Protein Structures

All TopologiesAll Topologies/ Topologies+ Topologies

Categorized and clustered in:CATHSCOPFSSP

©CMBI 2002

-Topologies

The four-helix bundle

Myohemerythrin

©CMBI 2002

-Topologies

sandwiches and barrels

Immunoglobulin fold forms a sandwich

Plastocyanin contains barrel

©CMBI 2002

/ Topologies

/ - mixture of and

unit present in nucleotide binding proteins is named the Rossmann FoldExample: Flavodoxin

/ BarrelExample: TIM triose phosphate isomerase, “TIM-barrel”

©CMBI 2002

+ Topologies

+ - both and , but located in different domains

Examples:

Ribonuclease HCarbonic AnhydraseSerine protease inhibitor

©CMBI 2002

Quarternary Structure

Units of tertiary structure aggregate to form homo- or hetero- multimers.

The individual chains are called subunits or monomers.

The subunits (polypeptide chains) may be identical (e.g. TIM dimer) or non-identical (e.g. haemoglobin is a tetramer and contains 2 + 2 subunits).

Summary of Levels of Protein Structure

©George Helmkamp, Jr.