The structural switch of nucleotide-free kinesin

Kinesin-1 is an ATP-dependent motor protein that moves towards microtubules (+)-ends. Whereas structures of isolated ADP-kinesin and of complexes with tubulin of apo-kinesin and of ATP-like-kinesin are available, structural data on apo-kinesin-1 in the absence of tubulin are still missing, leaving t...

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Bibliographic Details
Published in:Scientific reports 2017-02, Vol.7 (1), p.42558-42558, Article 42558
Main Authors: Cao, Luyan, Cantos-Fernandes, Soraya, Gigant, Benoît
Format: Article
Language:English
Subjects:
38/70
631/45/535/1266
631/80/128/1923
Adenosine diphosphate
Adenosine Diphosphate - chemistry
Adenosine Diphosphate - metabolism
ATP
Biochemistry
Biochemistry, Molecular Biology
Cellular Biology
Humanities and Social Sciences
Humans
Kinesin
Kinesin - chemistry
Kinesin - genetics
Kinesin - metabolism
Life Sciences
Magnesium
Microtubules
Microtubules - chemistry
Microtubules - metabolism
Models, Biological
Models, Molecular
Molecular Conformation
Motor task performance
multidisciplinary
Mutation
Nucleotides - chemistry
Nucleotides - metabolism
Protein Binding
Science
Structural Biology
Tubulin
Tubulin - chemistry
Tubulin - metabolism
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Summary:Kinesin-1 is an ATP-dependent motor protein that moves towards microtubules (+)-ends. Whereas structures of isolated ADP-kinesin and of complexes with tubulin of apo-kinesin and of ATP-like-kinesin are available, structural data on apo-kinesin-1 in the absence of tubulin are still missing, leaving the role of nucleotide release in the structural cycle unsettled. Here, we identified mutations in the kinesin nucleotide-binding P-loop motif that interfere with ADP binding. These mutations destabilize the P-loop (T87A mutant) or magnesium binding (T92V), highlighting a dual mechanism for nucleotide release. The structures of these mutants in their apo form are either isomorphous to ADP-kinesin-1 or to tubulin-bound apo-kinesin-1. Remarkably, both structures are also obtained from the nucleotide-depleted wild-type protein. Our results lead to a model in which, when detached from microtubules, apo-kinesin possibly occupies the two conformations we characterized, whereas, upon microtubule binding, ADP-kinesin converts to the tubulin-bound apo-kinesin conformation and releases ADP. This conformation is primed to bind ATP and, therefore, to run through the natural nucleotide cycle of kinesin-1.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep42558