Different ways to depict a protein structure
Wire diagram
Ribbon diagram
Ball & stick of
featured area
Blue: positive
Red: negative
Space filling:
van der Waals
Surface
representation
(GRASP image)
Petsko G.A., Ringe, D., Protein Structure and Function 2004, figure 5-5, pg. 173.
Primary Structure:
Amino Acid Sequence
•
Enter Somethign
Model of HIV protease
http://mgl.scripps.edu/projects/tangible_models/movies
Tertiary Structure: An Example of an
All-Alpha Protein, Hemoglobin Subunit
Rotated 90 Degrees
Tertiary Structure: An Example of an
All-Beta Protein, Flu Virus Neuraminidase
1) Rotate 90 Degrees
Tertiary Structure: An Example of an
Alpha/Beta Protein, Triose Phosphate Isomerase
1) Rotate 90 Degrees
Tertiary Structure: An Example of an
Alpha + Beta Protein, TATA Binding Protein
1) Rotate 90 Degrees
From Tertiary to Quaternary Structure:
Hemoglobin as an Example
•
Quaternary structure -- the relative arrangement of
two or more individual polypeptide chains
•
Protein assemblies can contain one type of polypeptide
(homo-oligomer) or multiple types (hetero-oligomer)
•
Example: Hemoglobin (oxygen carrier in blood)
•
Hemoglobin is a hetero-tetramer composed of two
alpha subunits and two beta subunits
Hemoglobin, Tertiary Structure
Hemoglobin, Quaternary Structure
Tetrameric Hemoglobin
Single Subunit
Proteins: Sequence --> Structure --> Function
Anfinsen Experiment:
Denature ribonuclease (RNase)
Remove denaturant
Assay for RNase activity -- does the protein regain its 3-D
structure and its enzymatic activity?
Molecular chaperones - Anfinsen cages for folding proteins
Xu et al., 1997, Nature 388: 741
GroEL-GroES-(ADP)7 complex
Clicker question: A good design for a stable folded protein is…
1) A polar/charged core with mostly nonpolar residues on the surface.
2) A nonpolar core with mostly polar/charged residues on the surface.
3) An even mix of polar/charged and nonpolar residues in the core and
on the surface.
4) Fatty acids on the inside,
ribonucleotides on the outside.
5) Ralph Lauren.
Clicker question: A good design for a stable folded protein is…
A) A polar/charged core with mostly nonpolar residues on the surface.
B) A nonpolar core with mostly polar/charged residues on the surface.
C) An even mix of polar/charged and nonpolar residues in the core and
on the surface.
D) Fatty acids on the inside,
ribonucleotides on the outside.
E) Ralph Lauren.
The Protein Folding Problem: the sequence of a protein
cannot (yet) be used to predict its 3D structure
?
Protein Structure Prediction
“Critical Assessment of techniques for Structure
Prediction” (CASP 9) -- a competition
For more information or to enter, see
http://predictioncenter.org/
Winners earn an automatic “A+” in Bi 1
(retroactively, if necessary)
Inverse Protein Folding Problem
• Given a structure (or a functionality), identify an
amino acid sequence whose fold will be that
structure (exhibit that functionality).
• Can we make designer proteins with desired
functions?
Foldit
• New Nature Video - Foldit: Biology for gamers August 04, 2010
http://blogs.nature.com/news/thegreatbeyond/20
10/08/new_nature_video_foldit_biolog.html
• From David Baker’s webpage:
(http://depts.washington.edu/bakerpg/drupal/)
Foldit is a revolutionary new computer game enabling you to contribute to
important scientific research. Join this free online game and help us predict
the folds of unsolved proteins as well as designing new proteins to cure
diseases. We’re collecting data to find out if humans' pattern-recognition
and puzzle-solving abilities make them more efficient than existing
computer programs at pattern-folding tasks. If this turns out to be true,
we can then teach human strategies to computers and fold proteins better
than ever!