WFU Physics and Chemistry Colloquium

TITLE: Knots and Protein Folds

SPEAKER: Professor Patricia Jennings ,

TIME: Wednesday February 3, 2016 at 4:00 PM

PLACE: Room 101 Olin Physical Laboratory

Unexpectedly, proteins can tie themselves into knots in their native folds. Since protein folding from an unstructured polypeptide chain into the native-state is already complex, the existence of knotted polypeptide chains immediately raises the questions: how does the chain cross itself to form a knot and how does the knot affect function? To address these questions, we study two distinct classes of knotted proteins: the pierced lasso (PL) and deep-knotted trefoil methyltransferase (MT) families. We discovered the PL class of proteins, with leptin as the founding member. This growing class now includes well over 350 protein families, spanning a huge range of fold types and including all secondary structure elements. The PL topology in leptin is induced from the creation of a covalent loop via disulfide bond formation where part of the polypeptide chain is threaded through the loop, forming the characteristic knot and an elegant system for investigating threading mechanisms. Our newest combined experimental and theoretical studies of the monomeric MT proteins allow the investigation of the backbone knot in folding/unfolding and functional regulation. The goal of the current proposal is to use a multifaceted approach to investigate how the fundamental mechanisms of knotting/unknotting/threading are initiated and relate to overall protein folding, and how the knotted functional and folding landscapes are related.