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Autoinhibition of the kinesin-2 motor KIF17 via dual intramolecular mechanisms

Long-distance transport in cells is driven by kinesin and dynein motors that move along microtubule tracks. These motors must be tightly regulated to ensure the spatial and temporal fidelity of their transport events. Transport motors of the kinesin-1 and kinesin-3 families are regulated by autoinhi...

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Autores principales: Hammond, Jennetta W., Blasius, T. Lynne, Soppina, Virupakshi, Cai, Dawen, Verhey, Kristen J.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2886353/
https://www.ncbi.nlm.nih.gov/pubmed/20530208
http://dx.doi.org/10.1083/jcb.201001057
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author Hammond, Jennetta W.
Blasius, T. Lynne
Soppina, Virupakshi
Cai, Dawen
Verhey, Kristen J.
author_facet Hammond, Jennetta W.
Blasius, T. Lynne
Soppina, Virupakshi
Cai, Dawen
Verhey, Kristen J.
author_sort Hammond, Jennetta W.
collection PubMed
description Long-distance transport in cells is driven by kinesin and dynein motors that move along microtubule tracks. These motors must be tightly regulated to ensure the spatial and temporal fidelity of their transport events. Transport motors of the kinesin-1 and kinesin-3 families are regulated by autoinhibition, but little is known about the mechanisms that regulate kinesin-2 motors. We show that the homodimeric kinesin-2 motor KIF17 is kept in an inactive state in the absence of cargo. Autoinhibition is caused by a folded conformation that enables nonmotor regions to directly contact and inhibit the enzymatic activity of the motor domain. We define two molecular mechanisms that contribute to autoinhibition of KIF17. First, the C-terminal tail interferes with microtubule binding; and second, a coiled-coil segment blocks processive motility. The latter is a new mechanism for regulation of kinesin motors. This work supports the model that autoinhibition is a general mechanism for regulation of kinesin motors involved in intracellular trafficking events.
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spelling pubmed-28863532010-12-14 Autoinhibition of the kinesin-2 motor KIF17 via dual intramolecular mechanisms Hammond, Jennetta W. Blasius, T. Lynne Soppina, Virupakshi Cai, Dawen Verhey, Kristen J. J Cell Biol Research Articles Long-distance transport in cells is driven by kinesin and dynein motors that move along microtubule tracks. These motors must be tightly regulated to ensure the spatial and temporal fidelity of their transport events. Transport motors of the kinesin-1 and kinesin-3 families are regulated by autoinhibition, but little is known about the mechanisms that regulate kinesin-2 motors. We show that the homodimeric kinesin-2 motor KIF17 is kept in an inactive state in the absence of cargo. Autoinhibition is caused by a folded conformation that enables nonmotor regions to directly contact and inhibit the enzymatic activity of the motor domain. We define two molecular mechanisms that contribute to autoinhibition of KIF17. First, the C-terminal tail interferes with microtubule binding; and second, a coiled-coil segment blocks processive motility. The latter is a new mechanism for regulation of kinesin motors. This work supports the model that autoinhibition is a general mechanism for regulation of kinesin motors involved in intracellular trafficking events. The Rockefeller University Press 2010-06-14 /pmc/articles/PMC2886353/ /pubmed/20530208 http://dx.doi.org/10.1083/jcb.201001057 Text en © 2010 Hammond et al. https://creativecommons.org/licenses/by-nc-sa/3.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ (https://creativecommons.org/licenses/by-nc-sa/3.0/) ).
spellingShingle Research Articles
Hammond, Jennetta W.
Blasius, T. Lynne
Soppina, Virupakshi
Cai, Dawen
Verhey, Kristen J.
Autoinhibition of the kinesin-2 motor KIF17 via dual intramolecular mechanisms
title Autoinhibition of the kinesin-2 motor KIF17 via dual intramolecular mechanisms
title_full Autoinhibition of the kinesin-2 motor KIF17 via dual intramolecular mechanisms
title_fullStr Autoinhibition of the kinesin-2 motor KIF17 via dual intramolecular mechanisms
title_full_unstemmed Autoinhibition of the kinesin-2 motor KIF17 via dual intramolecular mechanisms
title_short Autoinhibition of the kinesin-2 motor KIF17 via dual intramolecular mechanisms
title_sort autoinhibition of the kinesin-2 motor kif17 via dual intramolecular mechanisms
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2886353/
https://www.ncbi.nlm.nih.gov/pubmed/20530208
http://dx.doi.org/10.1083/jcb.201001057
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