Structure of the GLD-1 Homodimerization Domain: Insights into STAR Protein-Mediated Translational Regulation

被引：20

作者：

Beuck, Christine ^{[1
,2
,3
]}

Szymczyna, Blair R. ^{[1
,2
,3
]}

Kerkow, Donald E. ^{[1
,2
,3
]}

Carmel, Andrew B. ^{[1
,2
,3
]}

Columbus, Linda ^{[4
]}

Stanfield, Robyn L. ^{[1
,2
,3
]}

Williamson, James R. ^{[1
,2
,3
]}

机构：

[1] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

[3] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[4] Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA

来源：

STRUCTURE | 2010年 / 18卷 / 03期

基金：

美国国家科学基金会;

关键词：

RNA-BINDING PROTEIN; BACKBONE DYNAMICS; CAENORHABDITIS-ELEGANS; SIGNAL-TRANSDUCTION; SEX DETERMINATION; KH-DOMAIN; F-BOX; NMR; FOG-2; IDENTIFICATION;

D O I：

10.1016/j.str.2009.12.016

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：

Posttranscriptional regulation of gene expression is an important mechanism for modulating protein levels in eukaryotes, especially in developmental pathways. The highly conserved homodimeric STAR/GSG proteins play a key role in regulating translation by binding bipartite consensus sequences in the untranslated regions of target mRNAs, but the exact mechanism remains unknown. Structures of STAR protein RNA binding subdomains have been determined, but structural information is lacking for the homodimerization subdomain. Here, we present the structure of the C. elegans GLD-1 homodimerization domain dimer, determined by a combination of X-ray crystallography and NMR spectroscopy, revealing a helix-turn-helix monomeric fold with the two protomers stacked perpendicularly. Structure-based mutagenesis demonstrates that the dimer interface is not easily disrupted, but the structural integrity of the monomer is crucial for GLD-1 dimerization. Finally, an improved model for STAR-mediated translational regulation of mRNA, based on the GLD-1 homodimerization domain structure, is presented.

引用

页码：377 / 389

页数：13

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