title: Direct visualization of myosin-binding protein C bridging myosin and actin filaments in intact muscle.
abstract: Myosin-binding protein C (MyBP-C) is a thick filament protein playing an essential role in muscle contraction, and MyBP-C mutations cause heart and skeletal muscle disease in millions worldwide. Despite its discovery 40 y ago, the mechanism of MyBP-C function remains unknown. In vitro studies suggest that MyBP-C could regulate contraction in a unique way--by bridging thick and thin filaments--but there has been no evidence for this in vivo. Here we use electron tomography of exceptionally well preserved muscle to demonstrate that MyBP-C does indeed bind to actin in intact muscle. This binding implies a physical mechanism for communicating the relative sliding between thick and thin filaments that does not involve myosin and which could modulate the contractile process.
authors.affiliation: Molecular Medicine Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom. p.luther@imperial.ac.uk
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Luther
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Winkler
authors.forename: Kenneth
authors.initials: K
authors.lastname: Taylor
authors.forename: Maria E
authors.initials: ME
authors.lastname: Zoghbi
authors.forename: Roger
authors.initials: R
authors.lastname: Craig
authors.forename: Raúl
authors.initials: R
authors.lastname: Padrón
authors.forename: John M
authors.initials: JM
authors.lastname: Squire
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D055592:Biophysical Phenomena; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D055032:Electron Microscope Tomography; D017110:Freeze Substitution; D006801:Humans; D021621:Imaging, Three-Dimensional; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D009218:Myosins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D011898:Ranidae; D000099163:Myosin Binding Protein C
chemical_list: D000199:Actins; D002352:Carrier Proteins; D009218:Myosins; D000099163:Myosin Binding Protein C