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

Publication ,  Journal Article
Schumacher, MA; Goodman, RH; Brennan, RG
Published in: J Biol Chem
November 10, 2000

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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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

November 10, 2000

Volume

275

Issue

45

Start / End Page

35242 / 35247

Location

United States

Related Subject Headings

  • Somatostatin
  • Signal Transduction
  • Sequence Homology, Amino Acid
  • Response Elements
  • Protein Structure, Secondary
  • Molecular Sequence Data
  • Models, Molecular
  • Magnesium
  • Lysine
  • Leucine Zippers
 

Citation

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Schumacher, M. A., Goodman, R. H., & Brennan, R. G. (2000). 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(45), 35242–35247. https://doi.org/10.1074/jbc.M007293200
Schumacher, M. A., R. H. Goodman, and R. G. Brennan. “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, no. 45 (November 10, 2000): 35242–47. https://doi.org/10.1074/jbc.M007293200.
Schumacher, M. A., et al. “The structure of a CREB bZIP.somatostatin CRE complex reveals the basis for selective dimerization and divalent cation-enhanced DNA binding.J Biol Chem, vol. 275, no. 45, Nov. 2000, pp. 35242–47. Pubmed, doi:10.1074/jbc.M007293200.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

November 10, 2000

Volume

275

Issue

45

Start / End Page

35242 / 35247

Location

United States

Related Subject Headings

  • Somatostatin
  • Signal Transduction
  • Sequence Homology, Amino Acid
  • Response Elements
  • Protein Structure, Secondary
  • Molecular Sequence Data
  • Models, Molecular
  • Magnesium
  • Lysine
  • Leucine Zippers