The actin side-binding domain of gelsolin also caps actin filaments. Implications for actin filament severing

J Biol Chem. 1994 Apr 1;269(13):9473-9.

Abstract

Gelsolin is an actin filament-severing and -capping protein which is inhibited by polyphosphoinositides (PPI). Severing requires gelsolin binding to the side of the filaments through a site in segments 2 and 3 (S2-3) to position another site in segment 1 (S1) to sever filaments. In this paper, we report that S2-3, like S1, caps actin filaments. Since neither S1 and S2-3 caps as well as gelsolin, and neither severs actin filament, S2-3 may actively contribute to severing by capping filaments cooperatively with S1. We used deletional mutagenesis to locate the S2-3 sequence required for actin filament side binding, capping, and PPI binding and found that these sites are located close to the NH2 terminus of S2 (residues 161-172). S3, a segment which has no known function up to now and does not by itself bind actin, contributes to stable capping and may contain an additional PPI-binding site.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism*
  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • Cloning, Molecular
  • Gelsolin / chemistry
  • Gelsolin / isolation & purification
  • Gelsolin / metabolism*
  • Kinetics
  • Molecular Sequence Data
  • Mutagenesis
  • Neomycin / pharmacology
  • Oligodeoxyribonucleotides
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositol Phosphates / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Restriction Mapping
  • Sequence Deletion

Substances

  • Actins
  • Gelsolin
  • Oligodeoxyribonucleotides
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositol Phosphates
  • Recombinant Proteins
  • Neomycin