Molecular origin of the weak susceptibility of kinesin velocity to loads and its relation to the collective behavior of kinesins

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dc.citation.firstpageE8611en_US
dc.citation.issueNumber41en_US
dc.citation.journalTitlePNASen_US
dc.citation.lastpageE8617en_US
dc.citation.volumeNumber114en_US
dc.contributor.authorWang, Qianen_US
dc.contributor.authorDiehl, Michael R.en_US
dc.contributor.authorJana, Bimanen_US
dc.contributor.authorCheung, Margaret S.en_US
dc.contributor.authorKolomeisky, Anatoly B.en_US
dc.contributor.authorOnuchic, José Nelsonen_US
dc.date.accessioned2017-11-15T14:12:33Zen_US
dc.date.available2017-11-15T14:12:33Zen_US
dc.date.issued2017en_US
dc.description.abstractMotor proteins are active enzymatic molecules that support important cellular processes by transforming chemical energy into mechanical work. Although the structures and chemomechanical cycles of motor proteins have been extensively investigated, the sensitivity of a motor’s velocity in response to a force is not well-understood. For kinesin, velocity is weakly influenced by a small to midrange external force (weak susceptibility) but is steeply reduced by a large force. Here, we utilize a structure-based molecular dynamic simulation to study the molecular origin of the weak susceptibility for a single kinesin. We show that the key step in controlling the velocity of a single kinesin under an external force is the ATP release from the microtubule-bound head. Only under large loading forces can the motor head release ATP at a fast rate, which significantly reduces the velocity of kinesin. It underpins the weak susceptibility that the velocity will not change at small to midrange forces. The molecular origin of this velocity reduction is that the neck linker of a kinesin only detaches from the motor head when pulled by a large force. This prompts the ATP binding site to adopt an open state, favoring ATP release and reducing the velocity. Furthermore, we show that two load-bearing kinesins are incapable of equally sharing the load unless they are very close to each other. As a consequence of the weak susceptibility, the trailing kinesin faces the challenge of catching up to the leading one, which accounts for experimentally observed weak cooperativity of kinesins motors.en_US
dc.identifier.citationWang, Qian, Diehl, Michael R., Jana, Biman, et al.. "Molecular origin of the weak susceptibility of kinesin velocity to loads and its relation to the collective behavior of kinesins." <i>PNAS,</i> 114, no. 41 (2017) National Academy of Sciences: E8611-E8617. https://doi.org/10.1073/pnas.1710328114.en_US
dc.identifier.digitalkinesin.submit.Final2en_US
dc.identifier.doihttps://doi.org/10.1073/pnas.1710328114en_US
dc.identifier.urihttps://hdl.handle.net/1911/98819en_US
dc.language.isoengen_US
dc.publisherNational Academy of Sciencesen_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the authors and published by PNAS.en_US
dc.subject.keywordcollective behavioren_US
dc.subject.keywordkinesinen_US
dc.subject.keywordmolecular mechanismen_US
dc.subject.keywordsusceptibilityen_US
dc.titleMolecular origin of the weak susceptibility of kinesin velocity to loads and its relation to the collective behavior of kinesinsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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