Journal of Proteomics & Bioinformatics
Open Access
ISSN: 0974-276X
+44 1223 790975
ISSN: 0974-276X
+44 1223 790975
Rebecca S Buckley, Victoria Dauphin, Davon Carter, Edward J Wojcik, Thomas M Huckaba and Sunyoung Kim
Louisiana State University School of Medicine & Health Sciences Center, USA
Xavier University of Louisiana, USA
Posters & Accepted Abstracts: J Proteomics Bioinform
In kinesins, loop-5 is implicated in mechanochemistry and widely noted for its allosteric druggability. Yet, its native role has been obscured by its sequence variability and irregular conformations: No signature sequence in function or ligand-binding has been defined. Here we hypothesize that the loop-5 protein backbone is shaped by small spatial motifs in a catalyticallydependent manner. Mining of small motifs, <5 residues in length and based on amide hydrogen-bonding and phi/psi angles showed that loop-5 of two different processive kinesin motor proteins have variable and conserved ordered structures that are not dependent on amino acid identity. Mutation of conserved, inter-linked loop-5 niches is shown to selectively deregulate mechanical output and catalysis of both motors. Analysis of 55 reported substitutions in 6 kinesins complemented our experiments; disruption of mechanochemical coupling is correlated with mutation in small motifs and not within classical secondary structures. Thus, loop-5 has a conserved function as a kinesin transducer but we redefine it as a series of variable and conserved 3D motif switches that can encode a spectrum of mechanocoupling strategies. Modular organization of a series of small spatial motifs is extendable to other loops in motor proteins specifically and NTPases more broadly.
Rebecca S Buckley has completed her PhD in 2016 from Louisiana State University Medical School & Health Sciences Center. She is currently a Postdoctoral fellow in the lab of Sunyoung Kim where she is continuing her work on the functional characterization of a surface-exposed, drug-binding loop and its role in kinesin mechanochemistry and oligomerization.
Email: RShea@lsuhsc.edu