Significance of Knotted Structures for Function of Proteins and Nucleic Acids - September 17-21, 2014

Significance of Knotted Structures for Function of Proteins and Nucleic Acids

Thursday Abstracts

Folding of Nascent Chains of Knotted Proteins Nicole Lim, Anna Mallam, Elin Sivertsson, Joe Rogers, Danny Hsu, Laura Itzhaki, Sophie Jackson . University of Cambridge, Cambridge, United Kingdom. Since 2000, when they were first identified by Willie Taylor, the number of knotted proteins within the pdb has increased and there are now nearly 300 such structures. The polypeptide chain of these proteins forms a topologically knotted structure. There are now examples of proteins which form simple 31 trefoil knots, 41, 52 Gordian knots and 61 Stevedore knots. Knotted proteins represent a significant challenge to both the experimental and computational protein folding communities. When and how the polypeptide chain knots during the folding of the protein poses an additional complexity to the folding landscape. We have been studying the structure, folding and function of two types of knotted proteins – the 31-trefoil knotted methyltransferases and 52-knotted ubiquitin C-terminal hydrolases. The talk will focus on our folding studies on knotted trefoil methyltransferases and will include our recent work using cell free in vitro translation systems to probe the folding of nascent chains of knotted proteins. This approach has also been used to show that GroEL/GroES play a role in the folding of these proteins in vivo. New results on the degradation of knotted proteins by the bacterial ClpXClpP system will be presented. Exploring the Coordinated Functional and Folding Landscapes of Knotted Proteins Patricia Jennings . UCSD, La Jolla, USA. Flexibility and conformational changes allow proteins to perform the biological processes, such as ligand binding, oligomerization, conformational rearrangements and catalysis. Modulation of the dynamic states within the folded ensemble of a protein connect folded (or unfolded) states with biological functional states. Therefore, the interplay between a protein’s structure, fold, and function add complexity to the already delicate heterogeneous energy balance between functional states. Clusters of frustrated interactions within various conformational states are beginning to be identified as regions within protein scaffolds that may correlate with functional regions. In our work we explore the hypothesis that regions with competing geometric restraints that result in frustrated regions on the energy landscape of a given protein have both folding and functional relevance. Of the structurally unique, yet significant knotted conformations available in nature, the SPOUT and cysteine knot classes, both demonstrate these coordinated, yet complex interactions and are the subject of our current explorations.

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