Transcript Secondary structure - Radboud Universiteit

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 bond
Oxygen 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-helices
β-strands
Turns
Loops
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 distribution
Hydrogen 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 sheet
Hydrophobicity distribution alternating
Parallel and anti-parallel strands & hydrogen bonding patterns
Bulges 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 -strands
There 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 multimers
The 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
14-3-3
ANK3
Death
DED
PH
PTB
ARM
EFH
SAM
BH1
C1
EH
EVH
SH2
C2
SH3
CARD
FYVE
PDZ
WD40
WW
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 3D
Protein subunits can fold up to form a quarternary structure
Sometimes monomer is not active, but quarternary structure is
Protein domains
“independent units” with own function& structure
Average size 100-150 aa
Lego blocks of nature
Look in Interpro to find info about domains in your protein