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TitleKinesin-binding protein remodels the kinesin motor to prevent microtubule binding.
Journal, issue, pagesSci Adv, Vol. 7, Issue 47, Page eabj9812, Year 2021
Publish dateNov 19, 2021
AuthorsApril L Solon / Zhenyu Tan / Katherine L Schutt / Lauren Jepsen / Sarah E Haynes / Alexey I Nesvizhskii / David Sept / Jason Stumpff / Ryoma Ohi / Michael A Cianfrocco /
PubMed AbstractKinesins 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.
External linksSci Adv / PubMed:34797717 / PubMed Central
MethodsEM (single particle)
Resolution3.8 - 4.9 Å
Structure data

24672

7rsi

EMDB-24672, PDB-7rsi:
The cryo-EM map of KIF18A bound to KIFBP
Method: EM (single particle) / Resolution: 4.9 Å

24677

7rsq

EMDB-24677, PDB-7rsq:
Cryo-EM structure of KIFBP core
Method: EM (single particle) / Resolution: 3.8 Å

24744

7ryp

EMDB-24744, PDB-7ryp:
Cryo-EM structure of KIFBP:KIF15
Method: EM (single particle) / Resolution: 4.8 Å

24745

7ryq

EMDB-24745, PDB-7ryq:
Cryo-EM map of KIFBP
Method: EM (single particle) / Resolution: 4.6 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM / Adenosine diphosphate

Source
  • homo sapiens (human)
KeywordsMOTOR PROTEIN / kinesin regualtion protein / kinesin regulation protein

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