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 journalArticlepeer-review

99 Citations (Scopus)


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
Issue number14
Publication statusPublished - Jul 21 2004
Externally publishedYes


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

ASJC Scopus subject areas

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


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