title: Calmodulin in complex with the first IQ motif of myosin-5a functions as an intact calcium sensor.
abstract: The motor function of vertebrate myosin-5a is inhibited by its tail in a Ca2+-dependent manner. We previously demonstrated that the calmodulin (CaM) bound to the first isoleucine-glutamine (IQ) motif (IQ1) of myosin-5a is responsible for the Ca2+-dependent regulation of myosin-5a. We have solved the crystal structure of a truncated myosin-5a containing the motor domain and IQ1 (MD-IQ1) complexed with Ca2+-bound CaM (Ca2+-CaM) at 2.5-Å resolution. Compared with the structure of the MD-IQ1 complexed with essential light chain (an equivalent of apo-CaM), MD-IQ1/Ca2+-CaM displays large conformational differences in IQ1/CaM and little difference in the motor domain. In the MD-IQ1/Ca2+-CaM structure, the N-lobe and the C-lobe of Ca2+-CaM adopt an open conformation and grip the C-terminal and the N-terminal portions of the IQ1, respectively. Remarkably, the interlobe linker of CaM in IQ1/Ca2+-CaM is in a position opposite that in IQ1/apo-CaM, suggesting that CaM flip-flops relative to the IQ1 during the Ca2+transition. We demonstrated that CaM continuously associates with the IQ1 during the Ca2+transition and that the binding of CaM to IQ1 increases Ca2+affinity and substantially changes the kinetics of the Ca2+transition, suggesting that the IQ1/CaM complex functions as an intact Ca2+sensor responding to distinct calcium signals.
authors.affiliation: Group of Cell Motility and Muscle Contraction, State Key Laboratory of Integrated Management of Insect Pests and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Shen
authors.affiliation: Group of Cell Motility and Muscle Contraction, State Key Laboratory of Integrated Management of Insect Pests and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Sanduo
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Group of Cell Motility and Muscle Contraction, State Key Laboratory of Integrated Management of Insect Pests and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Wen-Bo
authors.initials: WB
authors.lastname: Zhang
authors.affiliation: Group of Cell Motility and Muscle Contraction, State Key Laboratory of Integrated Management of Insect Pests and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Hai-Man
authors.initials: HM
authors.lastname: Zhang
authors.affiliation: Group of Cell Motility and Muscle Contraction, State Key Laboratory of Integrated Management of Insect Pests and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zekuan
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Biodynamic Optical Imaging Center, Peking University, Beijing 100871, China.
authors.forename: Qian Peter
authors.initials: QP
authors.lastname: Su
authors.affiliation: Biodynamic Optical Imaging Center, Peking University, Beijing 100871, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Sun
authors.affiliation: University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Beijing Key Laboratory of Noncoding RNA, Chinese Academy of Sciences Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Keqiong
authors.identifier: 0000-0001-6169-7049
authors.initials: K
authors.lastname: Ye
authors.affiliation: Group of Cell Motility and Muscle Contraction, State Key Laboratory of Integrated Management of Insect Pests and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; lixd@ioz.ac.cn.
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Li
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism*; D002151:Calorimetry; D018360:Crystallography, X-Ray; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D024701:Myosin Type V / Q000737:chemistry* / Q000378:metabolism*; D000072417:Protein Domains; D011817:Rabbits; D013050:Spectrometry, Fluorescence; D040681:Structural Homology, Protein; D014364:Tryptophan / Q000378:metabolism
chemical_list: D002147:Calmodulin; D014364:Tryptophan; D024701:Myosin Type V; D002118:Calcium
keywords: calcium; calmodulin; molecular motor; myosin-5a; regulation