Transcript d) Structural Proteins

Protein structure
Visualization
Molecular Story
Review “Central Dogma”:
Sequence  Structure  function
Sequence based analysis
Structure based analysis
Gene Sequence
Function
Protein Structure
(Genomics)
(Structural Genomics)
Genomics)
Sequence similarity
Conserved domain
Predict structure
Predict function
Primary Structure
Secondary Structure
Tertiary Structure
Quaternary Structure
Molecules
Protein
(Functional
Protein - Protein
Protein-DNA/RNA
Protein-Lipids
Protein-Small
Bio-information data collection methods and major databases
Genome sequencing  Genbank (www.ncbi.nih.gov)
Genechip  gene expression database
X-ray crystallography, NMR  protein structure database
( www.pdb.org)
2D gel, mass spectrometry  proteomics database
Literature db  PubMed (www.pubmed.org)
Inherent genetic disease db  OMIM (www.ncbi.nih.gov)
Structure based analysis  Molecular profile and story
Protein structure: Primary
Secondary
Tertiary -Folding
quaternary
Protein structure determination:
X-ray crystallography
NMR spectroscopy
Protein structure prediction:
Secondary structure prediction
Homology modeling
Protein structure analysis:
The structure character of the individual protein
The structural basis of the protein function
Protein family (based on conserved domain, motifs
to predict their functions)
Write the molecular profile and story
I. Protein Molecular Structure
a) Protein is a polymer of amino acids.
20 Amino Acids ( Functional Groups)
Peptide Bond Formation
c) The Secondary Structure and
Tertiary Structure of Protein
Elements of Secondary Structure:
Helix
β-Strand
Loop
Turn
Helix
β-Strand
in β-Sheet
Turn
Loop
Turn
Secondary Structure & Ramachandran
Plot
Ramachandran Plot of CDC42-RhoGDI Complex [PDB Code 1DOA]
Many alpha helices are
Amphipathic
100 degree per residue
Molscript Representations of
Typical Protein Architectures.
β 7 Propellor (2bbkH)
β Barrel (2por)
α 4-Layer Sandwich
(2dnjA)
Sandwich (2hlaB)
Molscript Representations of
Typical Protein Architectures.
α β Barrel (4timA)
α Helix Bundle (2ccy)
2 Solenoid (1tsp)
α Horseshoe (1bnh)
Schematic Illustrations of Isologous and
Heterologous Association between
Protein Subunits
c d
a b
a b
cd
b
a
c
d
a cd--cd b
b--a
b
a d c
Isologous
Association
Heterologous
Tetramer
-b
-d
a---b
c---d
a---- a
-b
c---d
Heterologous
Association
c
-
Examples of Protein Quarternary
Structure.
The Isologous tetrameric
structure of rabbit skeletal
muscle aldolase, with three
twofold symmetry axes
The prealbumin dimer, in
which arrows depict the βstrands. The two monomers
(left and right) associate to
extend the two β-sheets
DNA Quadruplex &
G Quartets
+
K
NMR Spectroscopy
Sample-Spectrum-Structure
Crystal
X-Ray Crystallography
Diffraction
Electron Density
Structure
Protein Function and Structure (Architecture)
a) Binding:
Protein-DNA: transcription factors, eg TATA binding protein (PDB 1tgh)
Protein-RNA: microRNA-target protein  RNAi function
Protein-small molecule: eg: Myoglobin-Heme/O2,Fe (PDB 1a6k)
drug-target protein binding
Protein-Protein: eg, chaperonin GroEL
b) Catalysis: Enzymes Catalyzes biochemical reactions
eg: DNA Polymerase catalyzes DNA replication (PDB 1pbx)
HIV protease cleaves protein catalyzing the HIV replication (PDB 1a8k)
c) Switching:
eg: small GTPase Ras is a ‘Molecular switch’ for cell growth,
GTP-bound, ‘ON’ (PDB 121p); GDP-bound, “off” (PDB 1pll)
d) Structural Proteins:
Silk: a stack of anti-parallel beta-sheets (PDB 1slk)
within a sheet: covalent bonding and hydrogen bond,
between sheets: Van der Waals force
F-actin: helical assemblies of actin and actin-associated proteins
 muscle contraction, cytoskeleton
The Second Project
Go to www.pdb.org,
a) Type a protein (or a disease) name, search for the structures
b) Download the structure text file, save it as a text file with .pdb
extension.
c) Input the xxx.pdb file to Pymol (download from www.pymol.org)
to see the molecular structure, notice its structural characters.
d) Read the major reference paper (from www.pubmed.org) for this
protein structure and the corresponding gene, summarize the
connection of the structure and the protein function. Write the
molecular story for this gene.