TY - JOUR
T1 - Actin capping protein and its inhibitor CARMIL
T2 - How intrinsically disordered regions function
AU - Takeda, Shuichi
AU - Koike, Ryotaro
AU - Nitanai, Yasushi
AU - Minakata, Shiho
AU - Maéda, Yuichiro
AU - Ota, Motonori
PY - 2011/6
Y1 - 2011/6
N2 - 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.
AB - 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.
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U2 - 10.1088/1478-3975/8/3/035005
DO - 10.1088/1478-3975/8/3/035005
M3 - Article
C2 - 21572169
AN - SCOPUS:79956194275
VL - 8
JO - Physical Biology
JF - Physical Biology
SN - 1478-3967
IS - 3
M1 - 035005
ER -