Molecular Architecture of the Autoinhibited Kinesin-1 Lambda Particle

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2022 Sep 16

PMID 36112680

Authors

Johannes F Weijman

Sathish K N Yadav

Katherine J Surridge

Jessica A Cross

Ufuk Borucu

Judith Mantell

Derek N Woolfson

Christiane Schaffitzel

Mark P Dodding

Affiliations

Soon will be listed here.

Abstract

Despite continuing progress in kinesin enzyme mechanochemistry and emerging understanding of the cargo recognition machinery, it is not known how these functions are coupled and controlled by the α-helical coiled coils encoded by a large component of kinesin protein sequences. Here, we combine computational structure prediction with single-particle negative-stain electron microscopy to reveal the coiled-coil architecture of heterotetrameric kinesin-1 in its compact state. An unusual flexion in the scaffold enables folding of the complex, bringing the kinesin heavy chain-light chain interface into close apposition with a tetrameric assembly formed from the region of the molecule previously assumed to be the folding hinge. This framework for autoinhibition is required to uncover how engagement of cargo and other regulatory factors drives kinesin-1 activation.

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