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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
45
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pubmed:dateCreated |
2000-11-27
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pubmed:databankReference |
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pubmed:abstractText |
The cAMP responsive element-binding protein (CREB) is central to second messenger regulated transcription. To elucidate the structural mechanisms of DNA binding and selective dimerization of CREB, we determined to 3.0 A resolution, the structure of the CREB bZIP (residues 283-341) bound to a 21-base pair deoxynucleotide that encompasses the canonical 8-base pair somatostatin cAMP response element (SSCRE). The CREB dimer is stabilized in part by ionic interactions from Arg(314) to Glu(319') and Glu(328) to Lys(333') as well as a hydrogen bond network that links the carboxamide side chains of Gln(322')-Asn(321)-Asn(321')-Gln(322). Critical to family selective dimerization are intersubunit hydrogen bonds between basic region residue Tyr(307) and leucine zipper residue Glu(312), which are conserved in all CREB/CREM/ATF-1 family members. Strikingly, the structure reveals a hexahydrated Mg(2+) ion bound in the cavity between the basic region and SSCRE that makes a water-mediated DNA contact. DNA binding studies demonstrate that Mg(2+) ions enhance CREB bZIP:SSCRE binding by more than 25-fold and suggest a possible physiological role for this ion in somatostatin cAMP response element and potentially other CRE-mediated gene expression.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/Asparagine,
http://linkedlifedata.com/resource/pubmed/chemical/Cations,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamine,
http://linkedlifedata.com/resource/pubmed/chemical/Ions,
http://linkedlifedata.com/resource/pubmed/chemical/Lysine,
http://linkedlifedata.com/resource/pubmed/chemical/Magnesium,
http://linkedlifedata.com/resource/pubmed/chemical/Somatostatin
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
275
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
35242-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10952992-Amino Acid Sequence,
pubmed-meshheading:10952992-Arginine,
pubmed-meshheading:10952992-Asparagine,
pubmed-meshheading:10952992-Cations,
pubmed-meshheading:10952992-Crystallography, X-Ray,
pubmed-meshheading:10952992-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:10952992-DNA,
pubmed-meshheading:10952992-DNA-Binding Proteins,
pubmed-meshheading:10952992-Dimerization,
pubmed-meshheading:10952992-Dose-Response Relationship, Drug,
pubmed-meshheading:10952992-Electrons,
pubmed-meshheading:10952992-Escherichia coli,
pubmed-meshheading:10952992-Glutamic Acid,
pubmed-meshheading:10952992-Glutamine,
pubmed-meshheading:10952992-Hydrogen Bonding,
pubmed-meshheading:10952992-Ions,
pubmed-meshheading:10952992-Kinetics,
pubmed-meshheading:10952992-Leucine Zippers,
pubmed-meshheading:10952992-Lysine,
pubmed-meshheading:10952992-Magnesium,
pubmed-meshheading:10952992-Models, Molecular,
pubmed-meshheading:10952992-Molecular Sequence Data,
pubmed-meshheading:10952992-Protein Structure, Secondary,
pubmed-meshheading:10952992-Response Elements,
pubmed-meshheading:10952992-Sequence Homology, Amino Acid,
pubmed-meshheading:10952992-Signal Transduction,
pubmed-meshheading:10952992-Somatostatin
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pubmed:year |
2000
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pubmed:articleTitle |
The structure of a CREB bZIP.somatostatin CRE complex reveals the basis for selective dimerization and divalent cation-enhanced DNA binding.
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pubmed:affiliation |
Department of Biochemistry and Molecular Biology and the Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201-3098, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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