PXD073177-1

PXD073177 is an original dataset announced via ProteomeXchange.

Title	Structural Basis of Kinesin-1 Autoinhibition and Its Control of Microtubule-Based Motility
Description	Kinesin-1 is the first identified microtubule-based motor protein that drives anterograde intracellular transport of diverse cargoes in eukaryotic cells. Defects in kinesin-1 activity have been implicated in various human neurological disorders and intracellular pathogens such as bacteria and viruses hijack its activity. Despite its importance, the molecular mechanisms governing kinesin-1 activation remains poorly understood. Here, we report a 8.6-Å cryo-EM electron microscopy structure of the autoinhibited kinesin-1 heterotetramer. Our structure reveals a complex 36-nm head-to-tail assembly composed of two kinesin heavy chains (KHC) and two light chains (KLC), where the self-folded dimeric KHCs are stabilized by asymmetrically arranged KLCs tetratricopeptide repeat (TPR) domains. This state inhibits kinesin motility by constraining the dimeric motor domains in a configuration that is incompatible with motility. Notably, our structure also shows that the dimeric KLC TPR cargo-binding domains are occluded, providing a structural basis for the autoinhibition of both motor activity and cargo binding.In addition to functional studies, we also applied crosslinking mass spectrometry (XLMS) to validate the autoinhibitory model.
HostingRepository	PRIDE
AnnounceDate	2026-06-03
AnnouncementXML	Submission_2026-06-03_11:50:49.283.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD073177
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Yuqi Tang
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: NEWT:562;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-16 13:23:31	ID requested
⏵ 1	2026-06-03 11:50:49	announced

10.6019/PXD073177;

submitter keyword: kinesin-1, structure, kinesin, KIF5b, plus-end directed, microtubule motor,cryo-EM, motor protein

Stephen D. Fried
contact affiliation	Associate Professor, Department of Chemistry Associate Professor, Thomas C. Jenkins Department of Biophysics Associate Professor, Department of Biology
contact email	sdfried@jhu.edu
lab head
Yuqi Tang
contact affiliation	Johns Hopkins University
contact email	ytang93@jh.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD073177
     1. Label: PRIDE project
     2. Name: Structural Basis of Kinesin-1 Autoinhibition and Its Control of Microtubule-Based Motility