The structure of gelsolin bound to ATP

Dunja Urosev, Qing Ma, Agnes L.C. Tan, Robert C. Robinson, Leslie D. Burtnick

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Calcium activation of the actin-modifying properties of gelsolin is sensitive to ATP. Here, we show that soaking calcium-free gelsolin crystals in ATP-containing media results in ATP occupying a site that spans the two pseudosymmetrical halves of the protein. ATP binding involves numerous polar and hydrophobic contacts and is identical for the two copies of gelsolin related by non-crystallographic symmetry within the crystal. The γ-phosphate of ATP participates in several charge-charge interactions consistent with the preference of gelsolin for ATP, as a binding partner, over ADP. In addition, disruption of the ATP-binding site through Ca2+ activation of gelsolin reveals why ATP binds more tightly to the inactive molecule, and suggests how the binding of ATP may modulate the sensitivity of gelsolin to calcium ions. Similarities between the ATP and PIP2 interactions with the C-terminal half of gelsolin are evident from their overlapping binding sites and in that both molecules bind more tightly in the absence of calcium ions. We propose a model for how PIP2 may bind to calcium-free gelsolin based on the ATP-binding site.

Original languageEnglish
Pages (from-to)765-772
Number of pages8
JournalJournal of Molecular Biology
Volume357
Issue number3
DOIs
Publication statusPublished - Mar 31 2006
Externally publishedYes

Fingerprint

Gelsolin
Adenosine Triphosphate
Calcium
Binding Sites
Ions
Adenosine Diphosphate
Actins

Keywords

  • Actin
  • ATP
  • Calcium
  • Gelsolin
  • PIP

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

The structure of gelsolin bound to ATP. / Urosev, Dunja; Ma, Qing; Tan, Agnes L.C.; Robinson, Robert C.; Burtnick, Leslie D.

In: Journal of Molecular Biology, Vol. 357, No. 3, 31.03.2006, p. 765-772.

Research output: Contribution to journalArticle

Urosev, D, Ma, Q, Tan, ALC, Robinson, RC & Burtnick, LD 2006, 'The structure of gelsolin bound to ATP', Journal of Molecular Biology, vol. 357, no. 3, pp. 765-772. https://doi.org/10.1016/j.jmb.2006.01.027
Urosev, Dunja ; Ma, Qing ; Tan, Agnes L.C. ; Robinson, Robert C. ; Burtnick, Leslie D. / The structure of gelsolin bound to ATP. In: Journal of Molecular Biology. 2006 ; Vol. 357, No. 3. pp. 765-772.
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