The Origin of Minus-end Directionality and Mechanochemistry of Ncd Motors
| dc.citation.firstpage | e1002783 | en_US |
| dc.citation.issueNumber | 11 | en_US |
| dc.citation.journalTitle | PLoS Computational Biology | en_US |
| dc.citation.volumeNumber | 8 | en_US |
| dc.contributor.author | Jana, Biman | en_US |
| dc.contributor.author | Hyeon, Changbong | en_US |
| dc.contributor.author | Onuchic, José N. | en_US |
| dc.contributor.org | Center for Theoretical Biological Physics | en_US |
| dc.date.accessioned | 2012-11-20T18:22:40Z | |
| dc.date.available | 2012-11-20T18:22:40Z | |
| dc.date.issued | 2012 | en_US |
| dc.description.abstract | Adaptation 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.terms | none | en_US |
| dc.identifier.citation | Jana, 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. | |
| dc.identifier.doi | http://dx.doi.org/10.1371/journal.pcbi.1002783 | en_US |
| dc.identifier.uri | https://hdl.handle.net/1911/68350 | |
| dc.language.iso | eng | en_US |
| dc.publisher | Public Library of Science | |
| dc.rights | This 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.uri | https://creativecommons.org/licenses/by/4.0/ | |
| dc.title | The Origin of Minus-end Directionality and Mechanochemistry of Ncd Motors | en_US |
| dc.type | Journal article | en_US |
| dc.type.dcmi | Text | en_US |
| dc.type.publication | publisher version | en_US |