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

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

Motifs & Domains Motif: ______________________ Eg. Helix-turn-helix Will not fold independently

Motifs & Domains Domain:________________ 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