The kinesin-1 motor protein is regulated by a direct interaction of its head and tail. Export

@article{citeulike:2942460, abstract = {Kinesin-1 is a molecular motor protein that transports cargo along microtubules. Inside cells, the vast majority of kinesin-1 is regulated to conserve ATP and to ensure its proper intracellular distribution and coordination with other molecular motors. Regulated kinesin-1 folds in half at a hinge in its coiled-coil stalk. Interactions between coiled-coil regions near the enzymatically active heads at the N terminus and the regulatory tails at the C terminus bring these globular elements in proximity and stabilize the folded conformation. However, it has remained a mystery how kinesin-1's microtubule-stimulated ATPase activity is regulated in this folded conformation. Here, we present evidence for a direct interaction between the kinesin-1 head and tail. We photochemically cross-linked heads and tails and produced an 8-A cryoEM reconstruction of the cross-linked head-tail complex on microtubules. These data demonstrate that a conserved essential regulatory element in the kinesin-1 tail interacts directly and specifically with the enzymatically critical Switch I region of the head. This interaction suggests a mechanism for tail-mediated regulation of the ATPase activity of kinesin-1. In our structure, the tail makes simultaneous contacts with the kinesin-1 head and the microtubule, suggesting the tail may both regulate kinesin-1 in solution and hold it in a paused state with high ADP affinity on microtubules. The interaction of the Switch I region of the kinesin-1 head with the tail is strikingly similar to the interactions of small GTPases with their regulators, indicating that other kinesin motors may share similar regulatory mechanisms.}, address = {Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611;}, author = {Dietrich, Kristen A A. and Sindelar, Charles V V. and Brewer, Paul D D. and Downing, Kenneth H H. and Cremo, Christine R R. and Rice, Sarah E E.}, citeulike-article-id = {2942460}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0803575105}, citeulike-linkout-1 = {http://www.pnas.org/content/105/26/8938.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/105/26/8938.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/18579780}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=18579780}, day = {25}, doi = {10.1073/pnas.0803575105}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {em, experiment, kinesin, motor, regulation}, month = {June}, posted-at = {2008-12-15 05:40:15}, priority = {2}, title = {The kinesin-1 motor protein is regulated by a direct interaction of its head and tail.}, url = {http://dx.doi.org/10.1073/pnas.0803575105}, year = {2008} }

TY - JOUR ID - citeulike:2942460 L3 - citeulike-article-id:2942460 N2 - Kinesin-1 is a molecular motor protein that transports cargo along microtubules. Inside cells, the vast majority of kinesin-1 is regulated to conserve ATP and to ensure its proper intracellular distribution and coordination with other molecular motors. Regulated kinesin-1 folds in half at a hinge in its coiled-coil stalk. Interactions between coiled-coil regions near the enzymatically active heads at the N terminus and the regulatory tails at the C terminus bring these globular elements in proximity and stabilize the folded conformation. However, it has remained a mystery how kinesin-1's microtubule-stimulated ATPase activity is regulated in this folded conformation. Here, we present evidence for a direct interaction between the kinesin-1 head and tail. We photochemically cross-linked heads and tails and produced an 8-A cryoEM reconstruction of the cross-linked head-tail complex on microtubules. These data demonstrate that a conserved essential regulatory element in the kinesin-1 tail interacts directly and specifically with the enzymatically critical Switch I region of the head. This interaction suggests a mechanism for tail-mediated regulation of the ATPase activity of kinesin-1. In our structure, the tail makes simultaneous contacts with the kinesin-1 head and the microtubule, suggesting the tail may both regulate kinesin-1 in solution and hold it in a paused state with high ADP affinity on microtubules. The interaction of the Switch I region of the kinesin-1 head with the tail is strikingly similar to the interactions of small GTPases with their regulators, indicating that other kinesin motors may share similar regulatory mechanisms. JF - Proceedings of the National Academy of Sciences of the United States of America SN - 1091-6490 AD - Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611; TI - The kinesin-1 motor protein is regulated by a direct interaction of its head and tail. KW - em KW - experiment KW - kinesin KW - motor KW - regulation AU - Dietrich, Kristen A AU - Sindelar, Charles V AU - Brewer, Paul D AU - Downing, Kenneth H AU - Cremo, Christine R AU - Rice, Sarah E PY - 2008/06/25/ UR - http://dx.doi.org/10.1073/pnas.0803575105 ER -