Completed Cells, Biochemistry & Physiology Genetics & Molecular Biology

Correlation between the cellular functions of the myosin family of molecular motors and their biochemical & structural properties.

In plain English

AI plain-English summary

Every muscle twitch, heartbeat, and cell division depends on a family of proteins called myosins—tiny molecular motors that haul cargo, sense tension, and generate force inside cells. Scientists understand one prototypical myosin well, but the other 20-plus subfamilies remain largely a black box: no one knows how the same basic motor mechanism is tweaked to perform such wildly different jobs, or how cells send the right signals to control them. This project aims to crack that code. The researchers will test a working hypothesis across more than a dozen different myosins from slime mould, fruit flies, and mammals. They will also develop new fast-reaction methods that can probe the fundamental molecular events of myosin on a sub-millisecond timescale using only microgram quantities of protein. Finally, they will identify the structural motifs linked to specific mechanical activities and regulatory signals. This is fundamental science with no immediate practical application. If successful, it would allow researchers to predict a myosin’s cellular function simply from its genetic sequence—a capability that does not exist today. Such understanding could eventually inform treatments for heart disease, deafness, and cancers, all of which involve myosin dysfunction.

View original technical description
Myosins are mechanochemical proteins (from >20 subfamilies) involved in a wide range of motor and tension sensing activities in eucaryotic cells. While we have a good understanding of how the prototypical myosin works we do not understand how the same basic mechanism is adapted for the range of different activities that myosin is involved in, nor how the different regulatory signals operate on myosin within the cell. The specific aims are 1. to define the basic principles of how the motor ca n fulfils its different roles. To do this we have a working hypothesis which will be tested on more than a dozen different myosins across the myosin families I & II from Dictyostelium, Drosophila and mammals. 2. to continue to developed a novel series of fast reaction methods which allow use to probe the fundamental molecular events of myosin on a sub-millisecond time-scale using microgram quantities of protein. 3. to define the structural motifs associated with specific mechanical activity and specific regulatory signals. This results of this work will allow the cellular activity of a myosin to be predicted from the sequence and allow such predictions to be tested.

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Researchers

Michael Geeves (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Molecular mechanism of the myosin motor in skeletal muscle.
Regulatory Mechanisms in Myosins.
Regulation of myosin II filament assembly and stabilization, localization, and cortical anchoring .
Function of Nuclear Myosin Motors: A Biochemical and Single Molecule Characterization.
Bio-physical studies of motor proteins

Original classification

Programme Grant

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