Crystal structure of the actin binding domain of the cyclase-associated protein

Tetyana Dodatko, Alexander A. Fedorov, Marcin Grynberg, Yury Patskovsky, Denise A. Rozwarski, Lukasz Jaroszewski, Eliah Aronoff-Spencer, Elena Kondraskina, Tom Irving, Adam Godzik, Steven C. Almo

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Cyclase-associated protein (CAP or Srv2p) is a modular actin monomer binding protein that directly regulates filament dynamics and has been implicated in a number of complex developmental and morphological processes, including mRNA localization and the establishment of cell polarity. The crystal structure of the C-terminal dimerization and actin monomer binding domain (C-CAP) reveals a highly unusual dimer, composed of monomers possessing six coils of right-handed β-helix flanked by antiparallel β-strands. Domain swapping, involving the last two strands of each monomer, results in the formation of an extended dimer with an extensive interface. This structural and biochemical characterization provides new insights into the organization and potential mechanistic properties of the multiprotein assemblies that integrate dynamic actin processes into the overall physiology of the cell. An unanticipated finding is that the unique tertiary structure of the C-CAP monomer provides a structural model for a wide range of molecules, including RP2 and cofactor C, proteins involved in X-linked retinitis pigmentosa and tubulin maturation, respectively, as well as several uncharacterized proteins that exhibit very diverse domain organizations. Thus, the unusual right-handed β-helical fold present in C-CAP appears to support a wide range of biological functions.

Original languageEnglish (US)
Pages (from-to)10628-10641
Number of pages14
JournalBiochemistry
Volume43
Issue number33
DOIs
StatePublished - Aug 24 2004

ASJC Scopus subject areas

  • Biochemistry

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    Dodatko, T., Fedorov, A. A., Grynberg, M., Patskovsky, Y., Rozwarski, D. A., Jaroszewski, L., Aronoff-Spencer, E., Kondraskina, E., Irving, T., Godzik, A., & Almo, S. C. (2004). Crystal structure of the actin binding domain of the cyclase-associated protein. Biochemistry, 43(33), 10628-10641. https://doi.org/10.1021/bi049071r