Publication Date:
1995-10-13
Description:
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 A. 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 degree 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, T -- Stark, M R -- Johnson, A D -- Wolberger, C -- GM-37049/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Oct 13;270(5234):262-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7569974" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Crystallography, X-Ray
;
DNA, Fungal/*chemistry/metabolism
;
Fungal Proteins/*chemistry/metabolism
;
Homeodomain Proteins/*chemistry/metabolism
;
Hydrogen Bonding
;
Macromolecular Substances
;
Models, Molecular
;
Molecular Sequence Data
;
Nucleic Acid Conformation
;
Operator Regions, Genetic
;
Protein Conformation
;
Protein Folding
;
Protein Structure, Secondary
;
Protein Structure, Tertiary
;
Repressor Proteins/*chemistry/metabolism
;
Saccharomyces cerevisiae/*chemistry/genetics
;
*Saccharomyces cerevisiae Proteins
;
Transcription, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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