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
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
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
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
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
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).
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
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
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