Studies on the formation of DNA·protein interfaces: DNA specificity and straightening by CREB
| Autor: | Mary Kay Hamm, Alanna Schepartz |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
biology
Chemistry Base pair Binding protein Organic Chemistry Clinical Biochemistry Activating transcription factor Pharmaceutical Science CREB environment and public health Biochemistry Molecular biology ATF/CREB chemistry.chemical_compound Drug Discovery Transcriptional regulation biology.protein Molecular Medicine Molecular Biology Transcription factor DNA |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 5:1621-1626 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/0960-894x(95)00266-v |
| Popis: | Transcriptional regulation by bZIP proteins in the CREB/ATF family requires that these proteins discriminate between the CRE and AP-1 target sites, two DNA sequences that differ by a single G·C base pair. We reported recently that CRE-BP1, one member of the CREB/ATF family, prefers the CRE target site to the AP-1 target site by 2.3 kcal·mol −1 and straightens the intrinsic bend in its specific CRE target site upon binding. Of all well-characterized members of the CREB/ATF family, the cyclic-AMP response-element binding protein (CREB) is among the most divergent from CRE-BP1 in primary sequence. Here we show that CREB, like CRE-BP1, (1) displays high selectivity ( ΔΔG 0 obs = 1.5 kcal·mol −1 ) for the CRE target site and (2) straightens the intrinsically bent CRE target site upon binding. Although the effect of CREB on DNA conformation is comparable to that of CRE-BP1, the relative affinities of these two proteins for the CRE and AP-1 target sites are not. These results indicate that CRE/AP-1 specificity, the hallmark of the CREB/ATF transcription factor family, cannot be explained solely on the basis of differential DNA flexibility. |
| Databáze: | OpenAIRE |
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