title: Actin capping protein and its inhibitor CARMIL: how intrinsically disordered regions function.
abstract: The actin capping protein (CP) tightly binds to the barbed end of actin filaments to block further elongation. The β-tentacle in CP is an important region that ensures stable interaction with actin filaments. CARMIL inhibits the interaction of CP with actin filaments via the C-terminal portion containing the CP-binding motif, located in an intrinsically disordered region. We have proposed an allosteric inhibition model in which CARMIL suppresses CP by the population shift mechanism. Here, we solved a crystal structure of CP in complex with a CARMIL-derived peptide, CA32. The new structure clearly represents the α-helical form of the β-tentacle that was invisible in other CP/CARMIL peptide complex structures. In addition, we exhaustively performed a normal mode analysis with the elastic network model on all available crystal structures of the CP/CARMIL peptide complexes, including the new structure. We concluded that the CP-binding motif is necessary and sufficient for altering the fluctuation of CP, which is essential for attenuating the barbed-end-capping activity along the population shift mechanism. The roles and functions of the β-tentacle and the CP-binding motif are discussed in terms of their intrinsically disordered nature.
authors.affiliation: Structural Biology Research Center and Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Takeda
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Koike
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nitanai
authors.forename: Shiho
authors.initials: S
authors.lastname: Minakata
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Maéda
authors.forename: Motonori
authors.initials: M
authors.lastname: Ota
mesh_terms: D051344:Actin Capping Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D051344:Actin Capping Proteins; D002352:Carrier Proteins; D010455:Peptides