Molecular mechanisms of the interhead coordination by interhead tension in cytoplasmic dyneins

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dc.citation.firstpage10052en_US
dc.citation.issueNumber40en_US
dc.citation.journalTitlePNASen_US
dc.citation.lastpage10057en_US
dc.citation.volumeNumber115en_US
dc.contributor.authorWang, Qianen_US
dc.contributor.authorJana, Bimanen_US
dc.contributor.authorDiehl, Michael R.en_US
dc.contributor.authorCheung, Margaret S.en_US
dc.contributor.authorKolomeisky, Anatoly B.en_US
dc.contributor.authorOnuchic, José Nelsonen_US
dc.date.accessioned2018-11-15T17:16:02Zen_US
dc.date.available2018-11-15T17:16:02Zen_US
dc.date.issued2018en_US
dc.description.abstractCytoplasmic dyneins play a major role in retrograde cellular transport by moving vesicles and organelles along microtubule filaments. Dyneins are multidomain motor proteins with two heads that coordinate their motion via their interhead tension. Compared with the leading head, the trailing head has a higher detachment rate from microtubules, facilitating the movement. However, the molecular mechanism of such coordination is unknown. To elucidate this mechanism, we performed molecular dynamics simulations on a cytoplasmic dynein with a structure-based coarse-grained model that probes the effect of the interhead tension on the structure. The tension creates a torque that influences the head rotating about its stalk. The conformation of the stalk switches from the α registry to the β registry during the rotation, weakening the binding affinity to microtubules. The directions of the tension and the torque of the leading head are opposite to those of the trailing head, breaking the structural symmetry between the heads. The leading head transitions less often to the β registry than the trailing head. The former thus has a greater binding affinity to the microtubule than the latter. We measured the moment arm of the torque from a dynein structure in the simulations to develop a phenomenological model that captures the influence of the head rotating about its stalk on the differential detachment rates of the two heads. Our study provides a consistent molecular picture for interhead coordination via interhead tension.en_US
dc.identifier.citationWang, Qian, Jana, Biman, Diehl, Michael R., et al.. "Molecular mechanisms of the interhead coordination by interhead tension in cytoplasmic dyneins." <i>PNAS,</i> 115, no. 40 (2018) National Academy of Sciences of the United States of America: 10052-10057. https://doi.org/10.1073/pnas.1806688115.en_US
dc.identifier.digitalMolecularMechen_US
dc.identifier.doihttps://doi.org/10.1073/pnas.1806688115en_US
dc.identifier.urihttps://hdl.handle.net/1911/103329en_US
dc.language.isoengen_US
dc.publisherNational Academy of Sciences of the United States of Americaen_US
dc.rightsThis open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.subject.keywordcytoplasmic dyneinen_US
dc.subject.keywordinterhead coordinationen_US
dc.subject.keywordinterhead tensionen_US
dc.subject.keywordmolecular simulationen_US
dc.titleMolecular mechanisms of the interhead coordination by interhead tension in cytoplasmic dyneinsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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