CONFORMATIONAL AND FUNCTIONAL-STUDIES OF 3 GELSOLIN SUBDOMAIN-1 SYNTHETIC PEPTIDES AND THEIR IMPLICATION IN ACTIN POLYMERIZATION

Gelsolin, a calcium and inositol phospholipid-sensitive protein regula tes actin filament length. Its activity is complex (capping, severing, etc.) and is supported by several functional domains. The N-terminal domain alone (SI), in particular, is able to impede actin polymerizati on. Our investigations were attempted to precise this inhibitory proce ss by using synthetic peptides as models mimicking gelsolin SI activit y. Three peptides issued from S1 and located in gelsolin-actin interfa ces were synthesized. The peptides (15-28, 42-55, and 96-114 sequences ) were tested for their conformational and actin binding properties. A lthough the three peptides interact well with actin, only peptide 42-5 5 affects actin polymerization. A detailed kinetic study shows that th e latter peptide essentially inhibits the nucleation step during actin polymerization. In conclusion, the present work shows that the bindin g of a synthetic peptide to a small sequence located outside the actin -actin interface is essential in the actin polymerization process. (C) 1997 John Wiley & Sons, Inc.