CRYSTAL-STRUCTURE OF THE MATA1/MAT-ALPHA-2 HOMEODOMAIN HETERODIMER BOUND TO DNA

被引:232
作者
LI, T
STARK, MR
JOHNSON, AD
WOLBERGER, C
机构
[1] JOHNS HOPKINS UNIV, SCH MED, DEPT BIOPHYS & BIOPHYS CHEM, BALTIMORE, MD 21205 USA
[2] JOHNS HOPKINS UNIV, SCH MED, HOWARD HUGHES MED INST, BALTIMORE, MD 21205 USA
[3] UNIV CALIF SAN FRANCISCO, SCH MED, DEPT MICROBIOL & IMMUNOL, SAN FRANCISCO, CA 94143 USA
关键词
D O I
10.1126/science.270.5234.262
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The Saccharomyces cerevisiae MATa1 and MAT alpha 2 homeodomain proteins, which play a role in determining yeast cell type, form a heterodimer that binds DNA and represses transcription in a cell type-specific manner. Whereas the alpha 2 and a1 proteins on their own have only modest affinity for DNA, the a1/alpha 2 heterodimer binds DNA with high specificity and affinity. The three-dimensional crystal structure of the a1/alpha 2 homeodomain heterodimer bound to DNA was determined at a resolution of 2.5 Angstrom. The a1 and alpha 2 homeodomains bind in a head-to-tail orientation, with heterodimer contacts mediated by a 16-residue tail located carboxyl-terminal to the alpha 2 homeodomain. This tail becomes ordered in the presence of a1, part of it forming a short amphipathic helix that packs against the a1 homeodomain between helices 1 and 2. A pronounced 60 degrees bend is induced in the DNA, which makes possible protein-protein and protein-DNA contacts that could not take place in a straight DNA fragment. Complex formation mediated by flexible protein-recognition peptides attached to stably folded DNA binding domains may prove to be a general feature of the architecture of other classes of eukaryotic transcriptional regulators.
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页码:262 / 269
页数:8
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