Petsko G.A., Ringe, D., Protein Structure and Function 2004, figure 5-5, pg. 173. Different ways to...
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Transcript of Petsko G.A., Ringe, D., Protein Structure and Function 2004, figure 5-5, pg. 173. Different ways to...
Petsko G.A., Ringe, D., Protein Structure and Function 2004, figure 5-5, pg. 173.
Different ways to depict a protein structure
Wire diagram Ribbon diagramBall & stick of featured area
Space filling:van der Waals
Surface representation (GRASP image)
Blue: positiveRed: negative
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
• 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
From Tertiary to Quaternary Structure: Hemoglobin as an Example
Proteins: Sequence --> Structure --> Function
Anfinsen Experiment: Denature ribonuclease (RNase)Remove denaturantAssay for RNase activity -- does the protein regain its 3-D structure and its enzymatic activity?
GroEL-GroES-(ADP)7 complexXu et al., 1997, Nature 388: 741
Molecular chaperones - Anfinsen cages for folding proteins
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, seehttp://predictioncenter.org/
Winners earn an automatic “A+” in Bi 1 (retroactively, if necessary)
Inverse Protein Folding ProblemInverse 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/2010/08/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!