Mechanisms of kinesin control by kinesin binding protein

Award Number
Research Grant
Status / Stage
5 January 2022 -
11 February 2025
Duration (calculated)
03 years 01 months
Funding Amount
Funder/Grant study page
Contracted Centre
King's College London
Principal Investigator
Dr Joseph Atherton
PI Contact
WHO Catergories
Understanding Underlying Disease
Disease Type
Dementia (Unspecified)

CPEC Review Info
Reference ID689
ResearcherReside Team


Award NumberBB/V006568/1
Status / StageActive
Start Date20220105
End Date20250211
Duration (calculated) 03 years 01 months
Funder/Grant study pageBBSRC UKRI
Contracted CentreKing's College London
Funding Amount£575,405.00


Kinesin family molecular motors play essential roles during cell division, differentiation, and maturity, distributing cellular cargo and organising microtubule (MT) networks. In dividing cells, they are essential force providers, MT organisers and signalling hubs. In cell development and plasticity, they reorganise the MT scaffolding and specialise cellular subdomains with targeted cargo delivery. Kinesin dysregulation has been implicated in a wide range of animal and plant pathologies. Kinesin activity is tightly regulated in time and space by auto-inhibitory conformations, post-translational modifications and co-factor binding. Kinesin-binding protein (KBP) is an important, yet poorly understood regulatory co-factor found in early eukaryotes to humans that binds a subset of kinesin motor domains to inhibit MT association. Crucial roles for KBP have been identified in a variety of cellular processes including mitosis, organelle distribution, spermatogenesis and neuronal development. Illustrating KBP’s importance, gene variants cause Goldberg-Shprintzen syndrome and determine neuroblastoma prognosis. Despite the importance of KBP in eukaryotic cell fundamentals, the mechanisms behind KBP’s selective kinesin inhibitory function remain unknown. Furthermore, it is unclear how KBP is regulated itself, in order to temporally and spatially manage selected kinesin activities. This project aims to reveal the mechanisms behind KBP’s kinesin member selectivity and inhibition and KBP regulation. Towards these aims, the revolutionary structural technique of cryo-electron microscopy will be used alongside supporting methods to characterise KBP interactions with various kinesin motor domains, autoinhibited kinesins and active kinesin dimers as well as the modulation of these interactions by phosphorylation. Unearthing KBP’s mechanisms will fill a void in our understanding of kinesin regulation, a central aspect of eukaryotic cell function.


This project aims to reveal the mechanisms behind KBP’s kinesin member selectivity and inhibition and KBP regulation.