Evidence map›Paper›PMID 31084716›Full record

ArticleeLife2019

Neck linker docking is critical for Kinesin-1 force generation in cells but at a cost to motor speed and processivity.

Breane G Budaitis, Shashank Jariwala, Dana N Reinemann, Kristin I Schimert, Guido Scarabelli, Barry J Grant, David Sept, Matthew J Lang, Kristen J Verhey

Open access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

24 citing papers in PubMed, 42 citations in OpenAlex.

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  4. Tether-scanning the kinesin motor domain reveals a core mechanical action.Proceedings of the National Academy of Sciences of the United States of America · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Breane G BudaitisCellular and Molecular Biology Program, University of Michigan, Ann Arbor, United States.
Shashank Jariwala *Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States.
Dana N Reinemann *Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, United States.
Kristin I Schimert *Biophysics Program, University of Michigan, Ann Arbor, United States.ORCID 0000-0001-9209-7986
Guido ScarabelliDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States.
Barry J GrantDivision of Biological Sciences, Section of Molecular Biology, University of California, San Diego, San Diego, United States.
David SeptBiophysics Program, University of Michigan, Ann Arbor, United States.
Matthew J LangDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, United States.
Kristen J VerheyCellular and Molecular Biology Program, University of Michigan, Ann Arbor, United States.ORCID 0000-0001-9329-4981
University of Michigan · USVanderbilt University · USUniversity of California San Diego · US

Funding

CELLULAR AND MOLECULAR BIOLOGY AT MICHIGANT32GM007315 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTHENVEEDU, MANOJKUMAR A · 1985 to 2021
$12.8M
Kinesin Motors and Microtubule-based TraffickingR35GM131744 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Kristen J. Verhey · 2019 to 2026
$6.3M
Regulation of the molecular motor kinesin-IR01GM070862 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI VERHEY, KRISTEN J. · 2005 to 2018
$4.2M
Molecular Analysis of Chromosome SegregationR35GM130293 · NIGMS · UNIVERSITY OF WASHINGTON · PI DAVIS, TRISHA N. · 2019 to 2023
$3.5M
National Science Foundation 1256260National Science Foundation 1330792National Science Foundation 1445197NIGMS NIH HHS R01 GM070862NIGMS NIH HHS R35 GM130293NIGMS NIH HHS R35 GM131744NIGMS NIH HHS T32 GM007315NIH HHS R01GM070862NIH HHS T32GM007315
6 · The paper itself

Abstract

Kinesin force generation involves ATP-induced docking of the neck linker (NL) along the motor core. However, the roles of the proposed steps of NL docking, cover-neck bundle (CNB) and asparagine latch (N-latch) formation, during force generation are unclear. Furthermore, the necessity of NL docking for transport of membrane-bound cargo in cells has not been tested. We generated kinesin-1 motors impaired in CNB and/or N-latch formation based on molecular dynamics simulations. The mutant motors displayed reduced force output and inability to stall in optical trap assays but exhibited increased speeds, run lengths, and landing rates under unloaded conditions. NL docking thus enhances force production but at a cost to speed and processivity. In cells, teams of mutant motors were hindered in their ability to drive transport of Golgi elements (high-load cargo) but not peroxisomes (low-load cargo). These results demonstrate that the NL serves as a mechanical element for kinesin-1 transport under physiological conditions.

Indexed as

Adenosine TriphosphateAnimalsChlorocebus aethiopsCOS CellsKinesinsMolecular Dynamics SimulationMutagenesis, Site-DirectedMutant ProteinsProtein BindingProtein ConformationAdenosine TriphosphateKIF5C protein, ratKinesinsMutant Proteinscell biologycover-neck bundleforcekinesinmicrotubulemolecular biophysicsmolecular motorneck linkernonestructural biology

Identifiers

PMID31084716
PMCPMC6533058
OpenAlexW2946303320

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.