title: Slow skeletal muscle myosin-binding protein-C (MyBPC1) mediates recruitment of muscle-type creatine kinase (CK) to myosin.
abstract: Muscle contraction requires high energy fluxes, which are supplied by MM-CK (muscle-type creatine kinase) which couples to the myofibril. However, little is known about the detailed molecular mechanisms of how MM-CK participates in and is regulated during muscle contraction. In the present study, MM-CK is found to physically interact with the slow skeletal muscle-type MyBPC1 (myosin-binding protein C1). The interaction between MyBPC1 and MM-CK depended on the creatine concentration in a dose-dependent manner, but not on ATP, ADP or phosphocreatine. The MyBPC1-CK interaction favoured acidic conditions, and the two molecules dissociated at above pH 7.5. Domain-mapping experiments indicated that MM-CK binds to the C-terminal domains of MyBPC1, which is also the binding site of myosin. The functional coupling of myosin, MyBPC1 and MM-CK is further corroborated using an ATPase activity assay in which ATP expenditure accelerates upon the association of the three proteins, and the apparent K(m) value of myosin is therefore reduced. The results of the present study suggest that MyBPC1 acts as an adaptor to connect the ATP consumer (myosin) and the regenerator (MM-CK) for efficient energy metabolism and homoeostasis.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
authors.forename: Tong-Jin
authors.initials: TJ
authors.lastname: Zhao
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Yan-Song
authors.initials: YS
authors.lastname: Gao
authors.forename: Fan-Guo
authors.initials: FG
authors.lastname: Meng
authors.forename: Yong-Bin
authors.initials: YB
authors.lastname: Yan
authors.forename: Hai-Meng
authors.initials: HM
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D052283:Creatine Kinase, MM Form / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D057809:HEK293 Cells; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D051379:Mice; D018657:Muscle Fibers, Slow-Twitch / Q000201:enzymology / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D009218:Myosins / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D011999:Recruitment, Neurophysiological / Q000502:physiology; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D052283:Creatine Kinase, MM Form; D009218:Myosins; D000099163:Myosin Binding Protein C