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Louisiana Biomedical Research Network

Joseph Chaney

Link to Pubmed Publications

Xavier University of Louisiana


Project Title

Applying the Brakes : Understanding the Role of the Conformational Changes in the Kinesin-5


Mentor

Edward Wojcik, Louisiana State University Health New Orleans


Funding Periods

Pilot Project (May 1, 2021 - April 30, 2022)

Startup Project (May 1, 2018 - August 18, 2020)


Abstract


In processive kinesins, motor domains proceed forward in a hand-over-hand stepping fashion, while performing ATP hydrolysis. Several of these biological nanomotors have been identified as very promising targets for potential cancer therapy such as kinesin-5 and kinesin-6. Their promise as clinical targets come from the fact that they are involved only in metaphase and not interphase like some of the leading clinical drugs. However, the overall mechanism of inhibition in these targets needs further exploration. Inspection of the crystal structures of kinesin dimers reveals the addition of strands to the central b-sheet is found in one head and absent in the other; this previously unrecognized structural asymmetry between the two heads may suggest a regulatory mechanism. What has been ignored is that the docking of the NL and cover-neck to the motor head coordinates two strand additions to the central b-sheet. During docking the NL forms two b- strands, (b9 and b10, form a sheet with b0 of the cover-neck and (b-sheet of the central b-sheet, respectively. These structural changes in the neck-linker and cover-neck of Kinesin-5 have not been reported as there is currently no dimeric structure for this protein. Thus, the importance of establishing this conformational switch in Kinesin-5 requires additional experiments for understanding and molecular validation.