Professor Peter Knight
The Johns Hopkins University, MD, USA: Postdoctoral Research Fellow 1976-1981; ARC Meat Research Institute, Bristol: MRC Postdoctoral Training Fellow 1980-1982, Senior, then Principal Scientific Officer 1982-1990; Bristol University: Research Fellow 1991-1997; Leeds University: Lecturer 1997-2005, Reader 2005-2007, Professor of Molecular Contractility 2007-2017, Visiting Professor from 2017, Emeritus member Astbury Centre for Structural Molecular Biology from 2017.
I have been fascinated by motor proteins ever since an undergraduate practical class in phase contrast light microscopy where I saw myofibrils isolated from muscle contract when given ATP. Many questions entered my mind at that time: how could such a beautifully ordered structure assemble; how could its components turn over during the lifetime of the muscle cell; what molecular mechanism could convert chemical energy to mechanical force and movement?
Pursuing answers to these questions has drawn me into many collaborative projects where I have used a combination of whatever biochemical and structural methods might shed light. I have worked on the giant proteins titin and nebulin which act a templates for the precise assembly of the myofibril, and on the structure of the thick and thin filaments of muscle that interact to produce force. I have analysed how myosin molecules exchange into thick filaments in living muscle fibres. I have used X-ray diffraction of muscle fibres and electron microscopy of myosin and actin molecules to investigate the origins of movement. I have been able to exploit the diverse family of myosins that have been discovered in recent decades to get answers that were near-impossible using muscle myosin. It has been especially informative to use myosin-5 which can work as a single molecule to transport cargoes in the cell along actin filaments by walking along them.
An unexpected twist has been our discovery that some myosins incorporate a length of single alpha helix into the mechanical lever that amplifies small movements caused by ATP hydrolysis within the myosin motor domain into large movements along actin. This led us to realise that such SAH domains are widespread in the proteome, but we are far from understanding their roles, which are presumably diverse. We have explored the basis of the stability of SAH domains and their dynamics.
Movement and transport of a different kind is produced by dynein, a motor protein from a completely different evolutionary lineage from myosin. In the cell, this motor transports cargoes along microtubules rather than actin filaments. It is also responsible for the beating movement of animal cilia and flagella, such as in sperm cells. Using electron microscopy we were able to examine dynein structure in detail, describe the structural changes induced by ATP hydrolysis and see how a two headed dynein walked along the microtubule.
Motor proteins need to be regulated so that they are switched off when they are not needed. Our electron microscopy work has shown that for myosins this is achieved by the motor domains interacting with each other and/or with other parts of the molecule. A particularly satisfying mechanism is used by myosin-5: when the cargo-binding part of the molecule has no cargo it binds to the two motors and turns them off<h4>Research projects</h4> <p>Any research projects I'm currently working on will be listed below. Our list of all <a href="https://biologicalsciences.leeds.ac.uk/dir/research-projects">research projects</a> allows you to view and search the full list of projects in the faculty.</p>
- King's College London PhD Interactions between muscle proteins actin and myosin
- King's College London BSc Biology
- British Biophysical Society
Research groups and institutes
- Structural Biology