1gji: Difference between revisions
New page: left|200px<br /><applet load="1gji" size="450" color="white" frame="true" align="right" spinBox="true" caption="1gji, resolution 2.85Å" /> '''Crystal structure of... |
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[[Image:1gji.gif|left|200px]]<br /><applet load="1gji" size=" | [[Image:1gji.gif|left|200px]]<br /><applet load="1gji" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1gji, resolution 2.85Å" /> | caption="1gji, resolution 2.85Å" /> | ||
'''Crystal structure of c-Rel bound to DNA'''<br /> | '''Crystal structure of c-Rel bound to DNA'''<br /> | ||
==Overview== | ==Overview== | ||
BACKGROUND: The proto-oncogene product c-Rel is a Rel/NF-kappaB family | BACKGROUND: The proto-oncogene product c-Rel is a Rel/NF-kappaB family transcription factor that plays a critical role in lymphoid cell development and mediates CD28-induced expression of interleukin 2 (IL-2). The CD28 response element (CD28RE) in the IL-2 enhancer is nonameric and similar to the kappaB DNA target sites recognized by p65 homodimers. RESULTS: We have determined and refined the X-ray crystal structure of the c-Rel homodimer complexed to the CD28RE DNA site, 5'-AGAAATTCC-3', to 2.85 A resolution. The c-Rel homodimer binds CD28RE in a mode similar to that observed in the p65/IL-8 kappaB crystallographic complex. Binding studies reveal that the c-Rel homodimer recognizes the CD28RE with higher affinity as compared to other canonical kappaB sequences despite the nonconsensus A:T base pair at the 5' end of the CD28RE. Preferential recognition of the CD28RE by c-Rel results from the direct contacts between the protein and the DNA as well as intrasubunit interactions between the beta(f)-beta(g) loop in the dimerization domain and the DNA-contacting loop L1 of the N-terminal domain. Not only do these loops have different conformations in other Rel/DNA crystallographic complexes, but they also contain two of the five oncogenic point mutations found in v-Rel. CONCLUSIONS: The current structure indicates that a non-DNA-contacting loop in the dimerization domain and the DNA-contacting loop L1 may play critical roles in defining affinity and specificity. Two amino acid changes in these segments may account for the differential DNA binding by v-Rel as compared to that of c-Rel. | ||
==About this Structure== | ==About this Structure== | ||
1GJI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http:// | 1GJI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GJI OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Gallus gallus]] | [[Category: Gallus gallus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Chen, Y | [[Category: Chen, Y Q.]] | ||
[[Category: Ghosh, G.]] | [[Category: Ghosh, G.]] | ||
[[Category: Huang, D | [[Category: Huang, D B.]] | ||
[[Category: Phelps, C | [[Category: Phelps, C B.]] | ||
[[Category: Ruetsche, M.]] | [[Category: Ruetsche, M.]] | ||
[[Category: c-rel homodimer]] | [[Category: c-rel homodimer]] | ||
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[[Category: transcription factor]] | [[Category: transcription factor]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:50:44 2008'' | ||
Revision as of 10:50, 21 February 2008
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Crystal structure of c-Rel bound to DNA
Overview
BACKGROUND: The proto-oncogene product c-Rel is a Rel/NF-kappaB family transcription factor that plays a critical role in lymphoid cell development and mediates CD28-induced expression of interleukin 2 (IL-2). The CD28 response element (CD28RE) in the IL-2 enhancer is nonameric and similar to the kappaB DNA target sites recognized by p65 homodimers. RESULTS: We have determined and refined the X-ray crystal structure of the c-Rel homodimer complexed to the CD28RE DNA site, 5'-AGAAATTCC-3', to 2.85 A resolution. The c-Rel homodimer binds CD28RE in a mode similar to that observed in the p65/IL-8 kappaB crystallographic complex. Binding studies reveal that the c-Rel homodimer recognizes the CD28RE with higher affinity as compared to other canonical kappaB sequences despite the nonconsensus A:T base pair at the 5' end of the CD28RE. Preferential recognition of the CD28RE by c-Rel results from the direct contacts between the protein and the DNA as well as intrasubunit interactions between the beta(f)-beta(g) loop in the dimerization domain and the DNA-contacting loop L1 of the N-terminal domain. Not only do these loops have different conformations in other Rel/DNA crystallographic complexes, but they also contain two of the five oncogenic point mutations found in v-Rel. CONCLUSIONS: The current structure indicates that a non-DNA-contacting loop in the dimerization domain and the DNA-contacting loop L1 may play critical roles in defining affinity and specificity. Two amino acid changes in these segments may account for the differential DNA binding by v-Rel as compared to that of c-Rel.
About this Structure
1GJI is a Single protein structure of sequence from Gallus gallus. Full crystallographic information is available from OCA.
Reference
X-ray crystal structure of proto-oncogene product c-Rel bound to the CD28 response element of IL-2., Huang DB, Chen YQ, Ruetsche M, Phelps CB, Ghosh G, Structure. 2001 Aug;9(8):669-78. PMID:11587641
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