Molecular mechanism for kinesin-1 direct membrane recognition

Anton, Z.; Weijman, J. F.; Williams, C.; Moody, E. R. R.; Mantell, J.; Yip, Y. Y.; Cross, J. A.; Williams, T. A.; Steiner, R. A.; Crump, M.; Woolfson, D. N.; Dodding, M. P.

doi:10.1101/2021.01.20.427326

bioRxiv · 10.1101/2021.01.20.427326

Molecular mechanism for kinesin-1 direct membrane recognition

Anton, Z.·Weijman, J. F.·Williams, C.·Moody, E. R. R.·Mantell, J.·Yip, Y. Y.·Cross, J. A.·Williams, T. A.·Steiner, R. A.·Crump, M.·Woolfson, D. N.·Dodding, M. P.

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Abstract

The cargo-binding capabilities of cytoskeletal motor proteins have expanded during evolution through both gene duplication and alternative splicing. For the light chains of the kinesin-1 family of microtubule motors, this has resulted in an array of carboxy-terminal domain sequences of unknown molecular function. Here, combining phylogenetic analyses with biophysical, biochemical and cell biology approaches we identify a highly conserved membrane-induced curvature-sensitive amphipathic helix within this region of a newly defined subset of long kinesin light chain paralogues and splice isoforms. This helix mediates the direct binding of kinesin-1 to lipid membranes. Membrane binding requires specific anionic phospholipids and is important for kinesin-1 dependent lysosome positioning, a canonical activity that until now has been attributed exclusively the recognition of organelle-associated cargo adaptor proteins. This leads us to propose a new protein-lipid coincidence detection framework for kinesin-1 mediated organelle transport.

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Anton, Z., Weijman, J. F., Williams, C., Moody, E. R. R., Mantell, J., Yip, Y. Y., Cross, J. A., Williams, T. A., Steiner, R. A., Crump, M., Woolfson, D. N., Dodding, M. P.. 2021-01-21. Molecular mechanism for kinesin-1 direct membrane recognition. https://doi.org/10.1101/2021.01.20.427326

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