Download Protein Architecture and Structure Alignment

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project

Document related concepts

Ubiquitin wikipedia , lookup

Implicit solvation wikipedia , lookup

List of types of proteins wikipedia , lookup

Bimolecular fluorescence complementation wikipedia , lookup

Protein wikipedia , lookup

Rosetta@home wikipedia , lookup

Proteomics wikipedia , lookup

Protein moonlighting wikipedia , lookup

Protein design wikipedia , lookup

Western blot wikipedia , lookup

Circular dichroism wikipedia , lookup

Protein mass spectrometry wikipedia , lookup

Intrinsically disordered proteins wikipedia , lookup

Protein purification wikipedia , lookup

Cyclol wikipedia , lookup

Protein folding wikipedia , lookup

Structural alignment wikipedia , lookup

Protein domain wikipedia , lookup

Protein–protein interaction wikipedia , lookup

Alpha helix wikipedia , lookup

Homology modeling wikipedia , lookup

Nuclear magnetic resonance spectroscopy of proteins wikipedia , lookup

Protein structure prediction wikipedia , lookup

Transcript
Part I : Introduction to
Protein Structure
A/P Shoba Ranganathan
Kong Lesheng
National University of Singapore
Overview

Why protein structure?

The basics of protein

Levels of protein structure

Structural classification of protein structure
Why protein structure?




In the factory of living cells, proteins are the
workers, performing a variety of biological
tasks.
Each protein has a particular 3-D structure
that determines its function.
”Structure implies function”.
Structure is more conserved than sequence.
Protein structure is central for understanding
protein functions.
Sequence
Structure
Function
To understand functions, we need structures
α- conotoxin ImI and its three mutants
Rogers et al., 2000, JMB 304, 911
Anfinsen’s thermodynamic hypothesis
“The three-dimensional structure of a native protein
in its normal physiological milieu (solvent, pH, ionic
strength, presence of other components such as
metal ions or prosthetic groups, temperature, etc.)
is the one in which the Gibbs free energy of the
whole system is lowest; that is, that the native
conformation is determined by the totality of
interatomic interactions and hence by the amino
acid sequence, in a given environment.”
--- Anfinsen’s Nobel lecture, 1972
What drives protein folding?

Hydrophobic effects



Hydrophobic residues tend to be buried inside
Hydrophilic residues tend to be exposed to solvent
Hydrogen bonds help to stabilize the structure.
Overview

Why protein structure?

The basics of protein

Levels of protein structure

Structural classification of protein structure
The basics of protein




Proteins have one or more polypeptide chains
Building blocks: 20 amino acids.
Length range from 10 to 1000 residues.
Proteins fold into 3-D shape to perform
biological functions.
Common structure of Amino Acid
Cα is the chiral
center
Amino
H
H
+
N
R
Side chain = H,CH3,…
Atoms numbered b,g,d,e,z..
Ca
H
H
Backbone
O
C
-
O
Atom lost during
peptide bond
formation
Carboxylate
Aliphatic residues
Aromatic residues
Charged residues
Polar residues
S
The odd couple
Cg
Cb
Side chain = H
Cd
Ca
Ca
The peptide bonds
Coplanar atoms
Backbone torsion angles
Ramachandran / phi-psi plot
b-sheet
a-helix (left
handed)
y
a-helix
(right
handed)
f
Overview

Why protein structure?

The basics of protein

Levels of protein structure

Structural classification of protein structure
Primary structure

The amino acid sequences of
polypeptides chains.
Secondary structure

Local organization of protein backbone:
a-helix, b-strand (which assemble into
b-sheet), turn and interconnecting loop.
Ramachandran / phi-psi plot
b-sheet
a-helix (left
handed)
y
a-helix
(right
handed)
f
The a-helix

First structure to be predicted
(Pauling, Corey, Branson, 1951)
and experimentally solved
(Kendrew et al., 1958) –
myoglobin

One of the most closely packed
arrangement of residues.

3.6 residues per turn

5.4 Å per turn
The b-sheet

Backbone almost fully extended, loosely
packed arrangement of residues.
Topologies of b-sheets
Tertiary structure


Packing the secondary
structure elements into
a compact spatial unit.
“Fold” or domain– this
is the level to which
structure prediction is
currently possible.
Quaternary structure


Assembly of homo or
heteromeric protein
chains.
Usually the functional
unit of a protein,
especially for enzymes
Structure comparison facts



Proteins adopt only a limited number of folds.
Homologous sequences show very similar
structures: variations are mainly in non-conserved
regions.
There are striking regularities in the way in which
secondary structures are assembled (Levitt &
Chothia, 1976).
Overview

Why protein structure?

The basics of protein

Levels of protein structure

Structural classification of protein structure


There are two major databases for protein
structural classification: SCOP and CATH.
They have different classification hierarchy
and domain definitions.
SCOP

http://scop.mrc-lmb.cam.ac.uk/scop/

Structural Classification Of Proteins database

Classification is done manually

All nodes are annotated
SCOP at the top of the hierarchy
The hierarchy in SCOP
Root
Class
Fold
Superfamily
Family
Protein
5 classes: All-a, All-β, a/ β, a+ β,
multi-domain
Have the same major secondary
structure & topological connections
Probable common ancestry
Clear evolutionary relationship
CATH



http://www.biochem.ucl.ac.uk/bsm/cath
Class-Architecture-Topology-Homologous
superfamily
Manual classification at Architecture level but
automated at Topology level
The hierarchy in CATH
3 classes: Mainly-a, Mainly-β, a-β
Class
Architecture
Overall shape as determined by
orientations of secondary structures
Topology
Both the overall shape & connectivity
of secondary structure
Homologous
Superfamily
Sequence
Share a common ancestor
Classified based on sequence
identity