Biological role and structural mechanism of twinfilin-capping protein interaction

Sandra Falck, Ville O. Paavilainen, Martin A. Wear, J. Günter Grossmann, John A. Cooper, Pekka Lappalainen

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Twinfilin and capping protein (CP) are highly conserved actin-binding proteins that regulate cytoskeletal dynamics in organisms from yeast to mammals. Twinfilin binds actin monomer, while CP binds the barbed end of the actin filament. Remarkably, twinfilin and CP also bind directly to each other, but the mechanism and role of this interaction in actin dynamics are not defined. Here, we found that the binding of twinfilin to CP does not affect the binding of either protein to actin. Furthermore, site-directed mutagenesis studies revealed that the CP-binding site resides in the conserved C-terminal tail region of twinfilin. The solution structure of the twinfilin-CP complex supports these conclusions, in vivo, twinfilin's binding to both CP and actin monomer was found to be necessary for twinfilin's role in actin assembly dynamics, based on genetic studies with mutants that have defined biochemical functions. Our results support a novel model for how sequential interactions between actin monomers, twinfilin, CP, and actin filaments promote cytoskeletal dynamics.

Original languageEnglish
Pages (from-to)3010-3019
Number of pages10
JournalEMBO Journal
Volume23
Issue number15
DOIs
StatePublished - Aug 4 2004

Keywords

  • Actin
  • Capping protein
  • Twinfilin
  • Yeast

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