Structural basis for vertebrate filamin dimerization

被引:94
作者
Pudas, R
Kiema, TR
Butler, PJG
Stewart, M
Ylänne, J
机构
[1] Univ Oulu, Bioctr Oulu, Oulu, Finland
[2] Univ Oulu, Dept Biochem, Oulu, Finland
[3] MRC, Mol Biol Lab, Cambridge, England
基金
芬兰科学院;
关键词
D O I
10.1016/j.str.2004.10.014
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
Filamins are essential in cell motility and many developmental processes. They are large actin crosslinking proteins that contain actin binding domains in their N termini and a long rod region constructed from 24 tandem Ig domains. Dimerization is crucial for the actin crosslinking function of filamins and requires the most C-terminal Ig domain. We describe here the crystal structure of this 24th Ig domain (Ig24) of human filamin C and show how it mediates dimerization. The dimer interface is novel and quite different to that seen in the Dictyostelium discoideum filamin analog. The sequence signature of the dimerization interface suggests that the C-terminal domains of all vertebrate filamins share the same dimerization mechanism. Furthermore, we show that point mutations in the dimerization interface disrupt the dimer and that the dissociation constant for recombinant Ig24 is in the micromolar range.
引用
收藏
页码:111 / 119
页数:9
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