Structure of the N-terminal half of gelsolin bound to actin: Roles in severing, apoptosis and FAF

Leslie D. Burtnick, Dunja Urosev, Edward Irobi, Kartik Narayan, Robert C. Robinson

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

The actin filament-severing functionality of gelsolin resides in its N-terminal three domains (G1-G3). We have determined the structure of this fragment in complex with an actin monomer. The structure reveals the dramatic domain rearrangements that activate G1-G3, which include the replacement of interdomain interactions observed in the inactive, calcium-free protein by new contacts to actin, and by a novel G2-G3 interface. Together, these conformational changes are critical for actin filament severing, and we suggest that their absence leads to the disease Finnish-type familial amyloidosis. Furthermore, we propose that association with actin drives the calcium-independent activation of isolated G1-G3 during apoptosis, and that a similar mechanism operates to activate native gelsolin at micromolar levels of calcium. This is the first structure of a filament-binding protein bound to actin and it sets stringent, high-resolution limitations on the arrangement of actin protomers within the filament.

Original languageEnglish
Pages (from-to)2713-2722
Number of pages10
JournalEMBO Journal
Volume23
Issue number14
DOIs
Publication statusPublished - Jul 21 2004
Externally publishedYes

Fingerprint

Gelsolin
Actins
Apoptosis
Calcium
Actin Cytoskeleton
Protein Subunits
Carrier Proteins
Monomers
Chemical activation
Association reactions
Proteins

Keywords

  • Actin
  • Apoptosis
  • Familial amyloidosis
  • Gelsolin
  • X-ray crystallographic structure

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Structure of the N-terminal half of gelsolin bound to actin : Roles in severing, apoptosis and FAF. / Burtnick, Leslie D.; Urosev, Dunja; Irobi, Edward; Narayan, Kartik; Robinson, Robert C.

In: EMBO Journal, Vol. 23, No. 14, 21.07.2004, p. 2713-2722.

Research output: Contribution to journalArticle

Burtnick, Leslie D. ; Urosev, Dunja ; Irobi, Edward ; Narayan, Kartik ; Robinson, Robert C. / Structure of the N-terminal half of gelsolin bound to actin : Roles in severing, apoptosis and FAF. In: EMBO Journal. 2004 ; Vol. 23, No. 14. pp. 2713-2722.
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