@article {813, title = {Structure of the N-terminal half of gelsolin bound to actin: roles in severing, apoptosis and FAF}, journal = {Embo Journal}, volume = {23}, number = {14}, year = {2004}, note = {ISI Document Delivery No.: 847NBTimes Cited: 41Cited Reference Count: 59}, month = {Jul}, pages = {2713-2722}, type = {Article}, 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.}, keywords = {5-BISPHOSPHATE, actin, AMYLOIDOSIS-FINNISH TYPE, apoptosis, BINDING-SITE, CA2+ REGULATION, calcium, CRYSTAL-STRUCTURE, crystallographic structure, F-ACTIN, FAMILIAL AMYLOIDOSIS, FILAMENT BARBED ENDS, gelsolin, PHOSPHATIDYLINOSITOL 4, PLASMA GELSOLIN, X-RAY}, isbn = {0261-4189}, url = {://000223398800002}, author = {Burtnick, L. D. and Urosev, D. and Irobi, E. and Narayan, K. and Robinson, R. C.} }