title: Study of the mechanical properties of myomesin proteins using dynamic force spectroscopy.
abstract: Myomesin is the most prominent structural component of the sarcomeric M-Band that is expressed in mammalian heart and skeletal muscles. Like titin, this protein is an intracellular member of the Ig-fibronectin superfamily, which has a flexible filamentous structure and which is largely composed of two types of domain that are similar to immunoglobulin (Ig)-like and fibronectin type III (FNIII) domains. Several myomesin isoforms have been identified, and their expression patterns are highly regulated both spatially and temporally. Particularly, alternative splicing in the central part of the molecule gives rise to an isoform, EH (embryonic heart)-myomesin, containing a serine and proline-rich insertion with no well-defined secondary structure, the EH segment. EH-myomesin represents the major myomesin isoform at embryonic stages of mammalian heart and is rapidly down-regulated around birth, but it is re-expressed in the heart of patients suffering from dilated cardio-myopathy. Here, in order to facilitate a better understanding of the physiological, and possibly pathological, functions of myomesin proteins, we explore the mechanical stability, elasticity and force-driven structural changes of human myomesin's sub-molecular segments using single-molecule force spectroscopy and protein engineering. We find that human myomesin molecules are composed of modules (Ig and FNIII), that are designed to withstand force and we demonstrate that the human cardiac EH segment functions like an additional elastic stretch in the middle part of the EH-myomesin and behaves like a random coil. Consequently myomesin isoforms (proteins with or without the EH segment) have different elastic properties, the EH-myomesin being the more compliant one. These findings imply that the compliance of the M-band increases with the amount of EH-myomesin it contains. So, we provide the evidence that not only titin but also other sarcomeric proteins have complicated visco-elastic properties depending on the contractile parameters in different muscle types.
authors.affiliation: Institute of Physics, University of Basel, Klingelbergstrasse 82, CH-4056 Basel, Switzerland. Bertoncini.Patricia@wanadoo.fr
authors.forename: P
authors.initials: P
authors.lastname: Bertoncini
authors.forename: R
authors.initials: R
authors.lastname: Schoenauer
authors.forename: I
authors.initials: I
authors.lastname: Agarkova
authors.forename: M
authors.initials: M
authors.lastname: Hegner
authors.forename: J-C
authors.initials: JC
authors.lastname: Perriard
authors.forename: H-J
authors.initials: HJ
authors.lastname: Güntherodt
mesh_terms: D064211:Connectin; D004548:Elasticity; D005353:Fibronectins / Q000737:chemistry; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D018625:Microscopy, Atomic Force; D009124:Muscle Proteins / Q000737:chemistry* / Q000502:physiology*; D020033:Protein Isoforms / Q000737:chemistry / Q000502:physiology; D017434:Protein Structure, Tertiary
chemical_list: D064211:Connectin; D005353:Fibronectins; D007136:Immunoglobulins; D009124:Muscle Proteins; D020033:Protein Isoforms