1DH3

CRYSTAL STRUCTURE OF A CREB BZIP-CRE COMPLEX REVEALS THE BASIS FOR CREB FAIMLY SELECTIVE DIMERIZATION AND DNA BINDING

Summary for 1DH3

• Entry DOI: 10.2210/pdb1dh3/pdb
• Descriptor: DNA (5'-D(*CP*CP*TP*TP*GP*GP*CP*TP*GP*AP*CP*GP*TP*CP*AP*GP*CP*CP*AP*AP*G)-3'), TRANSCRIPTION FACTOR CREB, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: protein-dna complex, transcription-dna complex, transcription/dna
• Biological source: Mus musculus (house mouse)
• Cellular location: Nucleus: Q01147
• Total number of polymer chains: 4
• Total formula weight: 26246.26

Authors

Schumacher, M.A.,Goodman, R.H.,Brennan, R.G. (deposition date: 1999-11-27, release date: 2000-11-27, Last modification date: 2024-02-07)

Primary citation

Schumacher, M.A.,Goodman, R.H.,Brennan, R.G.
The structure of a CREB bZIP.somatostatin CRE complex reveals the basis for selective dimerization and divalent cation-enhanced DNA binding
J.Biol.Chem., 275:35242-35247, 2000

PubMed Abstract: 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.

PubMed: 10952992
DOI: 10.1074/jbc.M007293200

Experimental method

X-RAY DIFFRACTION (3 Å)