Regulatory Mechanisms in Myosins. (360G-Wellcome-094231_Z_10_Z)

£561,466

The programme aims to investigate the structure and function of a subset of myosins to determine how these proteins are regulated in vivo and in vitro, and thereby seek the underlying principles of regulation of biological movement. For myosins 2, 5 and 7 that we have shown to fold up into a compact, switched-off form, we will determine where activating partners bind and the structural changes they cause. We do not yet know whether myosins 1e, 9 and 10 use a compact form to regulate activity so we shall examine them to explore the diversity of control mechanisms myosins use. In addition we aim to exploit the specific, compact structure of the inhibited states of some myosins to discover the structure of whole myosins for the first time and at the highest resolution possible. We will use 3D reconstruction from cryo-EM images initially of whole myosins 2, 5 and 7 that we already know have a compact conformation. This will be complemented by crystallography of their tail domains to allow docking within the EM density envelope and an atomic scale appreciation of the regulatory interactions.

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Grant Details

Amount Awarded 561466
Applicant Surname Knight
Approval Committee Molecules, Genes and Cells Funding Committee
Award Date 2011-03-09T00:00:00+00:00
Financial Year 2010/11
Grant Programme: Title Project Grant
Internal ID 094231/Z/10/Z
Lead Applicant Prof Peter Knight
Other Applicant(s) Dr Stanley Burgess, Dr Thomas Edwards, Prof Michelle Peckham, Prof Neil Ranson
Partnership Value 561466
Planned Dates: End Date 2018-07-31T00:00:00+00:00
Planned Dates: Start Date 2012-02-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Yorkshire and the Humber