Publication Abstract from PubMed
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.
Structure of the N-terminal half of gelsolin bound to actin: roles in severing, apoptosis and FAF.,Burtnick LD, Urosev D, Irobi E, Narayan K, Robinson RC EMBO J. 2004 Jul 21;23(14):2713-22. Epub 2004 Jun 24. PMID:15215896[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
