Neck linker docking is critical for Kinesin-1 force generation in cells but at a cost to motor speed and processivity.
cell biology
cover-neck bundle
force
kinesin
microtubule
molecular biophysics
molecular motor
neck linker
none
structural biology
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
14 05 2019
14 05 2019
Historique:
received:
05
12
2018
accepted:
09
05
2019
pubmed:
16
5
2019
medline:
19
2
2020
entrez:
16
5
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31084716
doi: 10.7554/eLife.44146
pii: 44146
pmc: PMC6533058
doi:
pii:
Substances chimiques
Mutant Proteins
0
Adenosine Triphosphate
8L70Q75FXE
KIF5C protein, rat
EC 3.6.1.-
Kinesins
EC 3.6.4.4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Science Foundation
ID : 1445197
Pays : International
Organisme : NIGMS NIH HHS
ID : R35 GM131744
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM070862
Pays : United States
Organisme : National Science Foundation
ID : 1330792
Pays : International
Organisme : NIH HHS
ID : T32GM007315
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM130293
Pays : United States
Organisme : National Science Foundation
ID : 1256260
Pays : International
Organisme : NIH HHS
ID : R01GM070862
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007315
Pays : United States
Informations de copyright
© 2019, Budaitis et al.
Déclaration de conflit d'intérêts
BB, SJ, DR, KS, GS, BG, DS, ML, KV No competing interests declared
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