Project description
Exploring how Myo18 interposes into Myo2
The cytoskeleton, a protein network crucial for cellular structure, primarily consists of myosins. Among these, Myo18 stands out as a unique component. Unlike its counterparts, Myo18 does not generate force but rather acts as a cross-linker. On the other hand, Myo2, a member of a different myosin family, serves as the primary force producer in muscle sarcomeres and stress fibres. Understanding the interaction between these two myosin families poses a challenge. The MSCA-funded MyoDuo project aims to investigate Myo18’s cryptic cycle and function by characterising its structure in different nucleotide states of on/off actin and evaluating its interaction with Myo2 through their coiled-coil domains. Through biophysical studies, the project will explore how Myo18 intercalates into Myo2 filaments to alter force production and function.
Objective
The cytoskeleton is a complex protein web organised through the cell to provide structure and cell shape dynamics. One critical and often overlooked component is Myo18, which is part of the myosin superfamily of motor proteins. By interacting with actin, myosins canonically produce force through a series of conformational changes driven by the hydrolysis of ATP. However, Myo18 appears not to cycle through the set of conformations found for other myosins due to its divergent sequence. It is therefore hypothesised to act as an actin cross-linker rather than actively producing force. Another myosin family, Myo2, is the most prominent force producing component in the muscle sarcomere and in stress fibres which drive cell migration. Myo2 performs its role by forming filaments through a coiled coil domain creating a structure with multiple force producing heads ready to bind and move along actin. The coiled coil of Myo18 allows recruitment into Myo2 filaments within these niches but its role is obscure given its divergent behaviour. The sociology between these two myosin families, that is the specific interactions of different partners in space and time, is interesting given the complementary features of these two protein families. This study aims to structurally characterise Myo18 in different nucleotide states on and off actin to gain insights into the evolution and function of its cryptic cycle. Furthermore, this work will assess through structural characterisation how Myo18 and Myo2 directly interact through their coiled coil domains. This association will then be analysed through biophysical studies exploring how Myo18 alters force production and function by intercalating into Myo2 filaments.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
75231 Paris
France
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