title: A compact intermediate state of calmodulin in the process of target binding.
abstract: Calmodulin undergoes characteristic conformational changes by binding Ca(2+), which allows it to bind to more than 300 target proteins and regulate numerous intracellular processes in all eukaryotic cells. We measured the conformational changes of calmodulin upon Ca(2+) and mastoparan binding using the time-resolved small-angle X-ray scattering technique combined with flash photolysis of caged calcium. This measurement system covers the time range of 0.5-180 ms. Within 10 ms of the stepwise increase in Ca(2+) concentration, we identified a distinct compact conformational state with a drastically different molecular dimension. This process is too fast to study with a conventional stopped-flow apparatus. The compact conformational state was also observed without mastoparan, indicating that the calmodulin forms a compact globular conformation by itself upon Ca(2+) binding. This new conformational state of calmodulin seems to regulate Ca(2+) binding and conformational changes in the N-terminal domain. On the basis of this finding, an allosteric mechanism, which may have implications in intracellular signal transduction, is proposed.
authors.affiliation: SPring-8, Japan Synchrotron Radiation Research Institute, Kouto, Sayo, Hyogo 679-5198, Japan. teru@spring8.or.jp
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Yamada
authors.forename: Tatsuhito
authors.initials: T
authors.lastname: Matsuo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Iwamoto
authors.forename: Naoto
authors.initials: N
authors.lastname: Yagi
mesh_terms: D000085:Acetates / Q000737:chemistry; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry* / Q000378:metabolism*; D002417:Cattle; D005029:Ethylenediamines / Q000737:chemistry; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D012542:Scattering, Radiation; D014862:Wasp Venoms / Q000378:metabolism; D014965:X-Rays
chemical_list: D000085:Acetates; D002147:Calmodulin; D005029:Ethylenediamines; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014862:Wasp Venoms; C057014:DM-nitrophen; C037500:mastoparan; D002118:Calcium