Evidence map›Paper›PMID 32084356›Full record

ArticleStructure (London, England : 1993)2020

Structure of Microtubule-Trapped Human Kinesin-5 and Its Mechanism of Inhibition Revealed Using Cryoelectron Microscopy.

Alejandro Peña, Aaron Sweeney, Alexander D Cook, Julia Locke, Maya Topf, Carolyn A Moores

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Structure (London, England : 1993), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.4field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 34 citations in OpenAlex.

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  19. These motors were made for walking.Protein science : a publication of the Protein Society · 2020
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Alejandro PeñaInstitute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK.
Aaron SweeneyInstitute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK.
Alexander D CookInstitute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK.
Julia LockeInstitute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK.
Maya TopfInstitute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK.
Carolyn A MooresInstitute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK. Electronic address: c.moores@mail.cryst.bbk.ac.uk.
Institute of Structural and Molecular Biology · GB

Funding

Medical Research Council G0600084Medical Research Council MR/N009614/1Wellcome Trust 202679/Z/16/ZWellcome Trust 206166/Z/17/ZWellcome Trust 208398/Z/17/ZWellcome Trust 209250/Z/17/ZWorldwide Cancer Research 16-0037
6 · The paper itself

Abstract

Kinesin-5 motors are vital mitotic spindle components, and disruption of their function perturbs cell division. We investigated the molecular mechanism of the human kinesin-5 inhibitor GSK-1, which allosterically promotes tight microtubule binding. GSK-1 inhibits monomeric human kinesin-5 ATPase and microtubule gliding activities, and promotes the motor's microtubule stabilization activity. Using cryoelectron microscopy, we determined the 3D structure of the microtubule-bound motor-GSK-1 at 3.8 Å overall resolution. The structure reveals that GSK-1 stabilizes the microtubule binding surface of the motor in an ATP-like conformation, while destabilizing regions of the motor around the empty nucleotide binding pocket. Density corresponding to GSK-1 is located between helix-α4 and helix-α6 in the motor domain at its interface with the microtubule. Using a combination of difference mapping and protein-ligand docking, we characterized the kinesin-5-GSK-1 interaction and further validated this binding site using mutagenesis. This work opens up new avenues of investigation of kinesin inhibition and spindle perturbation.

Indexed as

Allosteric RegulationBinding SitesCryoelectron MicroscopyHumansKinesinsMicrotubulesMolecular Docking SimulationProtein BindingKIF11 protein, humanKinesinsantimitoticcryo-electron microscopyimage reconstructioninhibitorkinesinmicrotubule

Identifiers

PMID32084356
PMCPMC7139217
OpenAlexW3007339000

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.