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New page: left|200px<br /> <applet load="1nfa" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nfa" /> '''HUMAN TRANSCRIPTION FACTOR NFATC DNA BINDIN...
 
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[[Image:1nfa.gif|left|200px]]<br />
[[Image:1nfa.gif|left|200px]]<br /><applet load="1nfa" size="350" color="white" frame="true" align="right" spinBox="true"  
<applet load="1nfa" size="450" color="white" frame="true" align="right" spinBox="true"  
caption="1nfa" />
caption="1nfa" />
'''HUMAN TRANSCRIPTION FACTOR NFATC DNA BINDING DOMAIN, NMR, 10 STRUCTURES'''<br />
'''HUMAN TRANSCRIPTION FACTOR NFATC DNA BINDING DOMAIN, NMR, 10 STRUCTURES'''<br />


==Overview==
==Overview==
Transcription factors of the NFAT family regulate the production of, effector proteins that coordinate the immune response. The, immunosuppressive drugs FK506 and cyclosporin A (CsA) act by blocking a, Ca2+-mediated signalling pathway leading to NFAT. Although FK506 and CsA, have enabled human organs to be transplanted routinely, the toxic, side-effects of these drugs limit their usage. This toxicity might be, absent in antagonists that target NFAT directly. As a first step in the, structure-based search for NFAT antagonists, we now report the, identification and solution structure of a 20K domain of NFATc (NFATc-DBD), that is both necessary and sufficient to bind DNA and activate, transcription cooperatively. Although the overall fold of the NFATc, DNA-binding domain is related to that of NF-kappaB p50 (refs 2, 3), the, two proteins use significantly different strategies for DNA recognition., On the basis of these results, we present a model for the cooperative, complex formed between NFAT and the mitogenic transcription factor AP-1 on, the interleukin-2 enhancer.
Transcription factors of the NFAT family regulate the production of effector proteins that coordinate the immune response. The immunosuppressive drugs FK506 and cyclosporin A (CsA) act by blocking a Ca2+-mediated signalling pathway leading to NFAT. Although FK506 and CsA have enabled human organs to be transplanted routinely, the toxic side-effects of these drugs limit their usage. This toxicity might be absent in antagonists that target NFAT directly. As a first step in the structure-based search for NFAT antagonists, we now report the identification and solution structure of a 20K domain of NFATc (NFATc-DBD) that is both necessary and sufficient to bind DNA and activate transcription cooperatively. Although the overall fold of the NFATc DNA-binding domain is related to that of NF-kappaB p50 (refs 2, 3), the two proteins use significantly different strategies for DNA recognition. On the basis of these results, we present a model for the cooperative complex formed between NFAT and the mitogenic transcription factor AP-1 on the interleukin-2 enhancer.


==About this Structure==
==About this Structure==
1NFA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1NFA OCA].  
1NFA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NFA OCA].  


==Reference==
==Reference==
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Chen, L.]]
[[Category: Chen, L.]]
[[Category: Crabtree, G.R.]]
[[Category: Crabtree, G R.]]
[[Category: Dotsch, V.]]
[[Category: Dotsch, V.]]
[[Category: Ho, S.N.]]
[[Category: Ho, S N.]]
[[Category: Verdine, G.L.]]
[[Category: Verdine, G L.]]
[[Category: Wagner, G.]]
[[Category: Wagner, G.]]
[[Category: Wolfe, S.A.]]
[[Category: Wolfe, S A.]]
[[Category: You, A.]]
[[Category: You, A.]]
[[Category: Zhou, P.]]
[[Category: Zhou, P.]]
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[[Category: transcription regulation]]
[[Category: transcription regulation]]


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