1. Lecture 6 Web: pollev.com/ucibio Text: To: 37607 Type in: 169964

2. 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

3. Folding proteins Need precise shape – active site Amino acid sequence – determines folding Secondary structural elements form

4. Motifs & Domains Motif: Common structural element Eg. Helix-turn-helix Will not fold independently

5. Motifs & Domains Domain:Common structure Eg. Ig domain Folds independently

6. Working together Quaternary structure Multiple peptide chains interact Structure & function dependent on interactions

7. Quaternary structure

8. 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

9. Another protein folding experiment… TWO Sentences on Conclusions Upload into “Bio98 Folding expt” Midnight tonight

10. How do proteins find the “right” conformation? Every conformation = Gazillion years! Sequential stabilization of intermediates We DON’T KNOW tons!

11. Sequential stabilization of intermediates http://www.youtube.com/watch?v=YANAso8Jxrk

12. Protein folding: Another view http://www.youtube.com/watch?v=sD6vyfTtE4U

13. The importance of structure Why determine structure? Structure = Function Mechanism of function Rational drug design

14. The importance of protein structure “Chaperones” & protein folding Misfolded proteins are very, very bad! E.g. Huntington’s disease

15. Aggregation of mutant Huntington’s “Tag” protein - GFP Put “tagged” proteins in cells Compare: - Normal - Mutant

16. The importance of structure “Chaperones” & protein folding Misfolded proteins are very, very bad! E.g. Huntington’s disease E.g. Prions

17. 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

18. Practice exam Sent out No answers Discuss, Google, etc.