TY - JOUR
T1 - The structure of a CREB bZIP·somatostatin CRE complex reveals the basis for selective dimerization and divalent cation-enhanced DNA binding
AU - Schumacher, Maria A.
AU - Goodman, Richard H.
AU - Brennan, Richard G.
PY - 2000/11/10
Y1 - 2000/11/10
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M007293200
DO - 10.1074/jbc.M007293200
M3 - Article
C2 - 10952992
AN - SCOPUS:0034634671
SN - 0021-9258
VL - 275
SP - 35242
EP - 35247
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 45
ER -