The Origin of Minus-end Directionality and Mechanochemistry of Ncd Motors

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dc.citation.firstpagee1002783en_US
dc.citation.issueNumber11en_US
dc.citation.journalTitlePLoS Computational Biologyen_US
dc.citation.volumeNumber8en_US
dc.contributor.authorJana, Bimanen_US
dc.contributor.authorHyeon, Changbongen_US
dc.contributor.authorOnuchic, José N.en_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.date.accessioned2012-11-20T18:22:40Zen_US
dc.date.available2012-11-20T18:22:40Zen_US
dc.date.issued2012en_US
dc.description.abstractAdaptation of molecular structure to the ligand chemistry and interaction with the cytoskeletal filament are key to understanding the mechanochemistry of molecular motors. Despite the striking structural similarity with kinesin-1, which moves towards plus-end, Ncd motors exhibit minus-end directionality on microtubules (MTs). Here, by employing a structure-based model of protein folding, we show that a simple repositioning of the neck-helix makes the dynamics of Ncd non-processive and minus-end directed as opposed to kinesin-1. Our computational model shows that Ncd in solution can have both symmetric and asymmetric conformations with disparate ADP binding affinity, also revealing that there is a strong correlation between distortion of motor head and decrease in ADP binding affinity in the asymmetric state. The nucleotide (NT) free-ADP (?-ADP) state bound to MTs favors the symmetric conformation whose coiled-coil stalk points to the plus-end. Upon ATP binding, an enhanced flexibility near the head-neck junction region, which we have identified as the important structural element for directional motility, leads to reorienting the coiled-coil stalk towards the minus-end by stabilizing the asymmetric conformation. The minus-end directionality of the Ncd motor is a remarkable example that demonstrates how motor proteins in the kinesin superfamily diversify their functions by simply rearranging the structural elements peripheral to the catalytic motor head domain.en_US
dc.embargo.termsnoneen_US
dc.identifier.citationJana, Biman, Hyeon, Changbong and Onuchic, José N.. "The Origin of Minus-end Directionality and Mechanochemistry of Ncd Motors." <i>PLoS Computational Biology,</i> 8, no. 11 (2012) Public Library of Science: e1002783. http://dx.doi.org/10.1371/journal.pcbi.1002783.en_US
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pcbi.1002783en_US
dc.identifier.urihttps://hdl.handle.net/1911/68350en_US
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleThe Origin of Minus-end Directionality and Mechanochemistry of Ncd Motorsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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