Identification of a polyphosphoinositide-binding sequence in an actin monomer-binding domain of gelsolin

F. X. Yu, H. Q. Sun, P. A. Janmey, H. L. Yin

Research output: Contribution to journalArticle

200 Citations (Scopus)

Abstract

Gelsolin is an actin filament-severing and -capping protein that has profound effects on actin filament organization and assembly. It is activated by Ca2+ and inhibited by polyphosphoinositides (PPI). We have previously shown that PPI inhibit actin filament severing by the amino-terminal half of gelsolin and hypothesized that this is mediated through inhibition of actin filament side binding (by domains II-III of gelsolin), a requisite first step in severing. In this paper, we report that the subsequent step in severing, which is mediated by an actin monomer binding site located in domain I of gelsolin, is also regulated by PPI. We used deletional mutagenesis and a synthetic peptide to locate the sequence required for high affinity PPI binding in domain I. Our results show that the PPI-binding sequence has a basic charge distribution that is also present in the PPI-regulated actin filament side binding domain, and the two gelsolin PPI-binding sites have similar PPI-binding affinities. In addition, a similar motif is present in several other PPI-binding proteins, including a highly conserved region in the phospholipase C family. We propose that the sequences identified in gelsolin may represent a consensus for PPI binding in a variety of proteins.

Original languageEnglish (US)
Pages (from-to)14616-14621
Number of pages6
JournalJournal of Biological Chemistry
Volume267
Issue number21
StatePublished - 1992

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Gelsolin
Phosphatidylinositol Phosphates
Actins
Monomers
Actin Cytoskeleton
Actin Capping Proteins
Binding Sites
Mutagenesis
Charge distribution
Type C Phospholipases
Carrier Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Identification of a polyphosphoinositide-binding sequence in an actin monomer-binding domain of gelsolin. / Yu, F. X.; Sun, H. Q.; Janmey, P. A.; Yin, H. L.

In: Journal of Biological Chemistry, Vol. 267, No. 21, 1992, p. 14616-14621.

Research output: Contribution to journalArticle

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AU - Yin, H. L.

PY - 1992

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AB - Gelsolin is an actin filament-severing and -capping protein that has profound effects on actin filament organization and assembly. It is activated by Ca2+ and inhibited by polyphosphoinositides (PPI). We have previously shown that PPI inhibit actin filament severing by the amino-terminal half of gelsolin and hypothesized that this is mediated through inhibition of actin filament side binding (by domains II-III of gelsolin), a requisite first step in severing. In this paper, we report that the subsequent step in severing, which is mediated by an actin monomer binding site located in domain I of gelsolin, is also regulated by PPI. We used deletional mutagenesis and a synthetic peptide to locate the sequence required for high affinity PPI binding in domain I. Our results show that the PPI-binding sequence has a basic charge distribution that is also present in the PPI-regulated actin filament side binding domain, and the two gelsolin PPI-binding sites have similar PPI-binding affinities. In addition, a similar motif is present in several other PPI-binding proteins, including a highly conserved region in the phospholipase C family. We propose that the sequences identified in gelsolin may represent a consensus for PPI binding in a variety of proteins.

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