Repeat proteins: folding in parts, functioning as wholes

FERREIRO, DU

Banff

Workshop; 3rd Workshop in Stochasticity in Biochemical Reaction Networks; 2011

Banff International Research Station for Mathematical Innovation and Discovery

Repeat proteins are believed to be ancient folds. Instead of being formed by ?apparently random? amino-acid sequences, repeat-proteins are made up of tandem arrays of similar 20~40 amino-acid stretches that usually fold-up in elongated architectures. Quasi-one dimensional, these non-globular folds are stabilized only by interactions within each repeat or between adjacent repeats, with no obvious contacts between residues distant in sequence. Their ?biological function? is usually attributed as mediating specific protein-protein interactions, with a versatility for recognition paralleled to that of antibodies. Still, most of the natural repeat-proteins display strong couplings between distant functional sites, suggesting that specific binding is intimately coupled to strong structural transitions. Repeat proteins, by virtue of their inherent symmetries both in primary sequence and three dimensional structures, stand as remarkable models where the ?sequence-codes-folding-codes-function? hypothesis can be quantitatively evaluated. How many variables are needed to describe the ?functionally important motions? ? What are these and how to find them? Can they be traced back to the amino-acid sequences? I?ll discuss how the uncomplicated topology of repeat-proteins may facilitate the functional mapping of protein folding dynamics.