transport along microtubule / central nervous system projection neuron axonogenesis / mitochondrion transport along microtubule / kinesin binding / neuron projection maintenance / protein sequestering activity / microtubule cytoskeleton organization / in utero embryonic development / cytoskeleton / mitochondrion 類似検索 - 分子機能
KIF-1 binding protein / KIF-1 binding protein C terminal / Tetratricopeptide-like helical domain superfamily 類似検索 - ドメイン・相同性
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM094231
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM136822
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM121491
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM086610
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM111725
米国
引用
ジャーナル: Sci Adv / 年: 2021 タイトル: Kinesin-binding protein remodels the kinesin motor to prevent microtubule binding. 著者: April L Solon / Zhenyu Tan / Katherine L Schutt / Lauren Jepsen / Sarah E Haynes / Alexey I Nesvizhskii / David Sept / Jason Stumpff / Ryoma Ohi / Michael A Cianfrocco / 要旨: Kinesins are regulated in space and time to ensure activation only in the presence of cargo. Kinesin-binding protein (KIFBP), which is mutated in Goldberg-Shprintzen syndrome, binds to and inhibits ...Kinesins are regulated in space and time to ensure activation only in the presence of cargo. Kinesin-binding protein (KIFBP), which is mutated in Goldberg-Shprintzen syndrome, binds to and inhibits the catalytic motor heads of 8 of 45 kinesin superfamily members, but the mechanism remains poorly defined. Here, we used cryo–electron microscopy and cross-linking mass spectrometry to determine high-resolution structures of KIFBP alone and in complex with two mitotic kinesins, revealing structural remodeling of kinesin by KIFBP. We find that KIFBP remodels kinesin motors and blocks microtubule binding (i) via allosteric changes to kinesin and (ii) by sterically blocking access to the microtubule. We identified two regions of KIFBP necessary for kinesin binding and cellular regulation during mitosis. Together, this work further elucidates the molecular mechanism of KIFBP-mediated kinesin inhibition and supports a model in which structural rearrangement of kinesin motor domains by KIFBP abrogates motor protein activity.