Myosin S2- a strut or a spring? Structural and functional investigation of a "neglected" portion of the myosin molecule.

• Applicants: Professor Dr. Mathias Sebastian Gautel, from 1/2000 until 2/2003; Professor Dr. Roger S. Goody, since 2/2003
• Subject Area: Biochemistry
• Term: from 2000 to 2004
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5240974

Muscle myosin is two-headed, and this two-headedness emerges as an important functional feature. Mutations in the linking segment of myosin, S2, cause familiar hypertrophic cardiomyopathy (FHC). Despite this functional and medical importance of this region, there is no high-resolution structural or functional characterisation of S2. The aim of this collaborative proposal is to investigate the myosin head-tail junction and S2 segment functionally and structurally, gaining information on the coupling and communicating element of the two headed myosin-associated mutations. We will then introduce wild-type and mutant S2 into chimeric HMM fragments. These mutant and wild-type HMM fragments will be investigated by biophysical methods including in-vitro motility assays and photonic force microscopy between the two heads and S2. This should help to understand whether S2 is a rigid strut or a flexible link, and how changes in this structure, either by disease-associated mutation or by interacting proteins, can influence the mechanics of myosin.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1068: Molekulare Motoren