Structure of the N-terminal half of gelsolin bound to actin: roles in severing, apoptosis and FAF.
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.[1]References
- Structure of the N-terminal half of gelsolin bound to actin: roles in severing, apoptosis and FAF. Burtnick, L.D., Urosev, D., Irobi, E., Narayan, K., Robinson, R.C. EMBO J. (2004) [Pubmed]
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