title: Calmodulin bound to the first IQ motif is responsible for calcium-dependent regulation of myosin 5a.
abstract: Myosin 5a is as yet the best-characterized unconventional myosin motor involved in transport of organelles along actin filaments. It is well-established that myosin 5a is regulated by its tail in a Ca(2+)-dependent manner. The fact that the actin-activated ATPase activity of myosin 5a is stimulated by micromolar concentrations of Ca(2+) and that calmodulin (CaM) binds to IQ motifs of the myosin 5a heavy chain indicates that Ca(2+) regulates myosin 5a function via bound CaM. However, it is not known which IQ motif and bound CaM are responsible for the Ca(2+)-dependent regulation and how the head-tail interaction is affected by Ca(2+). Here, we found that the CaM in the first IQ motif (IQ1) is responsible for Ca(2+) regulation of myosin 5a. In addition, we demonstrate that the C-lobe fragment of CaM in IQ1 is necessary for mediating Ca(2+) regulation of myosin 5a, suggesting that the C-lobe fragment of CaM in IQ1 participates in the interaction between the head and the tail. We propose that Ca(2+) induces a conformational change of the C-lobe of CaM in IQ1 and prevents interaction between the head and the tail, thus activating motor function.
authors.affiliation: Group of Cell Motility and Muscle Contraction, National 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.forename: Mei
authors.initials: M
authors.lastname: Shen
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.forename: Hai-Man
authors.initials: HM
authors.lastname: Zhang
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Yao
authors.forename: Xiang-dong
authors.initials: XD
authors.lastname: Li
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D006801:Humans; D051379:Mice; D009218:Myosins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats
chemical_list: D002147:Calmodulin; D009218:Myosins; D002118:Calcium