Structure of the N-terminal half of gelsolin bound to actin: roles in severing, apoptosis and FAF

被引:99
作者
Burtnick, LD
Urosev, D
Irobi, E
Narayan, K
Robinson, RC
机构
[1] Uppsala Univ, Uppsala Biomed Ctr, Dept Med Biochem & Microbiol, S-75123 Uppsala, Sweden
[2] Univ British Columbia, Dept Chem, Vancouver, BC, Canada
[3] Univ British Columbia, Ctr Blood Res, Vancouver, BC V5Z 1M9, Canada
关键词
actin; apoptosis; familial amyloidosis; gelsolin; X-ray crystallographic structure;
D O I
10.1038/sj.emboj.7600280
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2713 / 2722
页数:10
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