Actin capping protein and its inhibitor CARMIL: How intrinsically disordered regions function

Shuichi Takeda, Ryotaro Koike, Yasushi Nitanai, Shiho Minakata, Yuichiro Maéda, Motonori Ota

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

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.

Original languageEnglish
Article number035005
JournalPhysical Biology
Volume8
Issue number3
DOIs
Publication statusPublished - Jun 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Actin capping protein and its inhibitor CARMIL: How intrinsically disordered regions function'. Together they form a unique fingerprint.

Cite this