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 language | English (US) |
|---|---|
| Pages (from-to) | 35242-35247 |
| Number of pages | 6 |
| Journal | Journal of Biological Chemistry |
| Volume | 275 |
| Issue number | 45 |
| DOIs | |
| State | Published - Nov 10 2000 |
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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 journal › Article
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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
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.
UR - http://www.scopus.com/inward/record.url?scp=0034634671&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034634671&partnerID=8YFLogxK
U2 - 10.1074/jbc.M007293200
DO - 10.1074/jbc.M007293200
M3 - Article
C2 - 10952992
AN - SCOPUS:0034634671
VL - 275
SP - 35242
EP - 35247
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 45
ER -