Multivariate Analysis of Conserved Sequence-Structure Relationships in Kinesins: Coupling of the Active Site and a Tubulin-binding Sub-domain Export

@article{citeulike:1260751, abstract = {An extensive computational analysis of available sequence and crystal structure data was used to identify functionally important residue interactions within the motor domain of the kinesin molecular motor. Principal component analysis revealed that all current kinesin crystal structures reside in one of two main conformations, which differ at the active site, and in the position of a microtubule-binding sub-domain relative to a rigid central core. This sub-domain consists of secondary structure elements [alpha]4-loop12-[alpha]5-loop13 and contains a conserved hydrophilic surface patch that may be involved in strong binding to microtubules. A hinge point for the sub-domain motion lies near a conserved glycine at position 292. Statistical coupling analysis revealed a network of co-evolving positions that link this region to the nucleotide-binding site, via a highly conserved histidine in the switch I loop. The data are consistent with a model in which the nucleotide status of the active site shifts kinesin between weak and strong binding conformations via reconfiguration of the identified sub-domain. Our data provide a statistically supported framework for further examination of this and other structure-function relationships in the kinesin family.}, author = {Grant, Barry J. and Mccammon, Andrew J. and Caves, Leo S. and Cross, Robert A.}, citeulike-article-id = {1260751}, citeulike-linkout-0 = {http://www.sciencedirect.com/science/article/B6WK7-4NCK2J1-1/2/f98ca3f420f69221036a0d0b05603259}, day = {18}, journal = {Journal of Molecular Biology}, keywords = {analysis, database, function, kinesin, motor, sequence}, month = {May}, number = {5}, pages = {1231--1248}, posted-at = {2007-05-07 10:32:20}, priority = {2}, title = {Multivariate Analysis of Conserved Sequence-Structure Relationships in Kinesins: Coupling of the Active Site and a Tubulin-binding Sub-domain}, url = {http://www.sciencedirect.com/science/article/B6WK7-4NCK2J1-1/2/f98ca3f420f69221036a0d0b05603259}, volume = {368}, year = {2007} }

TY - JOUR ID - citeulike:1260751 L3 - citeulike-article-id:1260751 N2 - An extensive computational analysis of available sequence and crystal structure data was used to identify functionally important residue interactions within the motor domain of the kinesin molecular motor. Principal component analysis revealed that all current kinesin crystal structures reside in one of two main conformations, which differ at the active site, and in the position of a microtubule-binding sub-domain relative to a rigid central core. This sub-domain consists of secondary structure elements [alpha]4-loop12-[alpha]5-loop13 and contains a conserved hydrophilic surface patch that may be involved in strong binding to microtubules. A hinge point for the sub-domain motion lies near a conserved glycine at position 292. Statistical coupling analysis revealed a network of co-evolving positions that link this region to the nucleotide-binding site, via a highly conserved histidine in the switch I loop. The data are consistent with a model in which the nucleotide status of the active site shifts kinesin between weak and strong binding conformations via reconfiguration of the identified sub-domain. Our data provide a statistically supported framework for further examination of this and other structure-function relationships in the kinesin family. IS - 5 JF - Journal of Molecular Biology EP - 1248 TI - Multivariate Analysis of Conserved Sequence-Structure Relationships in Kinesins: Coupling of the Active Site and a Tubulin-binding Sub-domain VL - 368 SP - 1231 KW - analysis KW - database KW - function KW - kinesin KW - motor KW - sequence AU - Grant, Barry AU - Mccammon, Andrew AU - Caves, Leo AU - Cross, Robert PY - 2007/05/18/ UR - http://www.sciencedirect.com/science/article/B6WK7-4NCK2J1-1/2/f98ca3f420f69221036a0d0b05603259 ER -