Lecture 6 Web: pollev.com/ucibio Text: To: Type in:
Lecture 6 objectives Understand how 2° structure leads to 3° structure Know the different interactions that stabilize structure Understand domains, motifs and their relationship to structure Understand the theory of local energy minimas in folding Understand formation of 4° structure Relate protein structure to function, and disease
Folding proteins Need precise shape – active site Amino acid sequence – determines folding Secondary structural elements form
Motifs & Domains Motif: Common structural element Eg. Helix-turn-helix Will not fold independently
Motifs & Domains Domain:Common structure Eg. Ig domain Folds independently
Working together Quaternary structure Multiple peptide chains interact Structure & function dependent on interactions
Quaternary structure
Another protein folding experiment… APX Normal activity250 units450 units +Heat5 units9 units +Heat +recovery188 units14 units +Protein “Y”244 units412 units +“Y” + heat7 units11 units +heat +Y +recovery198 units388 units
Another protein folding experiment… TWO Sentences on Conclusions Upload into “Bio98 Folding expt” Midnight tonight
How do proteins find the “right” conformation? Every conformation = Gazillion years! Sequential stabilization of intermediates We DON’T KNOW tons!
Sequential stabilization of intermediates
Protein folding: Another view
The importance of structure Why determine structure? Structure = Function Mechanism of function Rational drug design
The importance of protein structure “Chaperones” & protein folding Misfolded proteins are very, very bad! E.g. Huntington’s disease
Aggregation of mutant Huntington’s “Tag” protein - GFP Put “tagged” proteins in cells Compare: - Normal - Mutant
The importance of structure “Chaperones” & protein folding Misfolded proteins are very, very bad! E.g. Huntington’s disease E.g. Prions
MC questions in exam Question text T F ? A) Answer choice 1 T F ? B) Answer choice 2 T F ? C) Answer choice 3 T F ? D) Answer choice 4 Score ranges from -3 to +4
Practice exam Sent out No answers Discuss, Google, etc.