The structure of a CREB bZIP·somatostatin CRE complex reveals the basis for selective dimerization and divalent cation-enhanced DNA binding

Maria A. Schumacher, Richard Goodman, Richard G. Brennan

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

The cAMP responsive element-binding protein (CREB) is central to second messenger regulated transcription. To elucidate the structured mechanisms of DNA binding and selective dimerization of CREB, we determined to 3.0 Å 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 Arg314 to Glu319' and Glu328 to Lys333' as well as a hydrogen bond network that links the carboxamide side chains of Gln322'-Asn321-Asn321'-Gln322. Critical to family selective dimerization are intersubunit hydrogen bonds between basic region residue Tyr307 and leucine zipper residue Glu312, which are conserved in all CREB/CREM/ATF-1 family members. Strikingly, the structure reveals a hexahydrated Mg2+ ion bound in the cavity between the basic region and SSCRE that makes a water-mediated DNA contact. DNA binding studies demonstrate that Mg2+ 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.

Original languageEnglish (US)
Pages (from-to)35242-35247
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number45
DOIs
StatePublished - Nov 10 2000

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Dimerization
Divalent Cations
Carrier Proteins
Response Elements
Somatostatin
DNA
Ions
Base Pairing
Hydrogen
Hydrogen bonds
Leucine Zippers
Second Messenger Systems
Transcription
Gene expression
Dimers
Gene Expression
Water

ASJC Scopus subject areas

  • Biochemistry

Cite this

The structure of a CREB bZIP·somatostatin CRE complex reveals the basis for selective dimerization and divalent cation-enhanced DNA binding. / Schumacher, Maria A.; Goodman, Richard; Brennan, Richard G.

In: Journal of Biological Chemistry, Vol. 275, No. 45, 10.11.2000, p. 35242-35247.

Research output: Contribution to journalArticle

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