Journal of Proteomics & Bioinformatics
Open Access

Motor domain β-sheet motifs contribute to diversification of kinesin-microtubule interactions

6^th International Conference on Structural Biology

August 22-23, 2016 New Orleans, USA

Jessica Richard, Elizabeth D Kim, Victoria Dauphin, Minmin Luo, Rebecca S Buckley, C Parke, D Worthylake, Edward J Wojcik and Sunyoung Kim

Louisiana State University School of Medicine & Health Sciences Center, USA

Posters & Accepted Abstracts: J Proteomics Bioinform

Abstract :

There is a growing appreciation for the importance of correlated motions within �²-sheets of enzymatic proteins. Case in point, kinesin ATPases have �±/�² organization with a central �²-sheet that physically separates the two ligand-binding sites: The active and microtubule (MT)-binding sites. Meta-analysis of existing kinesin X-ray structures revealed that a change in motor function is correlated with a change in �²-sheet twist. We hypothesized that the change in twist was due to key sequence differences that occurred within the central �²-sheet during the evolution of the kinesin nanomotor. We first identified three �²-sheet motifs in which sequence changes correlate with different kinesin functional outputs. These motifs were structurally and functionally validated. X-ray structures of both �²-sheet substitution and an active site surface loop substitution were generated. We show that single-site substitution of the central �²-sheet results in loss of �²-strand and changes in twist that are propagated across the �²-sheet. Our functional assays provide evidence that these substitutions alter communication between the enzymeâ��s active and MT-binding sites. While correlated motions in �²-sheets are predominately studied in terms of backbone interactions, we show that side chain identity contributes to these motions. We conclude that �²-sheet sequence changes promote enzyme specialization and are likely a universal design principle in NTPases.

Biography :

Jessica Richard has completed her PhD in Biochemistry and Molecular Biology at Louisiana State University Health Sciences Center in New Orleans, LA in May 2016. She is currently a Post-doctoral fellow in the laboratory of Dr. Sunyoung Kim. She is investigating the evolution of sequence-structure-function relationships in kinesin motor proteins.

Email: jrick2@lsuhsc.edu