2jng

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==Overview==
==Overview==
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Cul7 is a member of the Cullin Ring Ligase (CRL) family and is required, for normal mouse development and cellular proliferation. Recently, a, region of Cul7 that is highly conserved in the p-53 associated, Parkin-like cytoplasmic protein, PARC, was shown to bind p53 directly., Here we identify the CPH domain (conserved domain within Cul7, PARC and, HERC2 proteins) of both Cul7 and PARC as a p53 interaction domain using, size exclusion chromatography and NMR spectroscopy. We present the first, structure of the evolutionary conserved CPH domain and provide novel, insight into the Cul7-p53 interaction. The NMR structure of the Cul7-CPH, domain reveals a fold similar to peptide interaction modules such as the, SH3, Tudor and KOW domains. The p53 interaction surface of both Cul7 and, PARC CPH domains was mapped to a conserved surface distinct from the, analogous peptide binding regions of SH3, KOW and Tudor domains, suggesting a novel mode of interaction. The CPH domain interaction surface, of p53 resides in the tetramerization domain and is formed by residues, contributed by at least two subunits.
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Cul7 is a member of the Cullin Ring Ligase (CRL) family and is required for normal mouse development and cellular proliferation. Recently, a region of Cul7 that is highly conserved in the p53-associated, Parkin-like cytoplasmic protein PARC, was shown to bind p53 directly. Here we identify the CPH domains (conserved domain within Cul7, PARC, and HERC2 proteins) of both Cul7 and PARC as p53 interaction domains using size exclusion chromatography and NMR spectroscopy. We present the first structure of the evolutionarily conserved CPH domain and provide novel insight into the Cul7-p53 interaction. The NMR structure of the Cul7-CPH domain reveals a fold similar to peptide interaction modules such as the SH3, Tudor, and KOW domains. The p53 interaction surface of both Cul7 and PARC CPH domains was mapped to a conserved surface distinct from the analogous peptide-binding regions of SH3, KOW, and Tudor domains, suggesting a novel mode of interaction. The CPH domain interaction surface of p53 resides in the tetramerization domain and is formed by residues contributed by at least two subunits.
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==Disease==
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Known disease associated with this structure: 3-M syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609577 609577]]
==About this Structure==
==About this Structure==
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==Reference==
==Reference==
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The conserved CPH domains of Cul7 and PARC are protein-protein interaction modules that bind the tetramerization domain of P53., Kaustov L, Lukin J, Lemak A, Duan S, Ho M, Doherty R, Penn LZ, Arrowsmith CH, J Biol Chem. 2007 Feb 12;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17298945 17298945]
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The conserved CPH domains of Cul7 and PARC are protein-protein interaction modules that bind the tetramerization domain of p53., Kaustov L, Lukin J, Lemak A, Duan S, Ho M, Doherty R, Penn LZ, Arrowsmith CH, J Biol Chem. 2007 Apr 13;282(15):11300-7. Epub 2007 Feb 12. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17298945 17298945]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Arrowsmith, C.H.]]
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[[Category: Arrowsmith, C H.]]
[[Category: Duan, S.]]
[[Category: Duan, S.]]
[[Category: Kaustov, L.]]
[[Category: Kaustov, L.]]
[[Category: Lemak, A.]]
[[Category: Lemak, A.]]
[[Category: Lukin, J.]]
[[Category: Lukin, J.]]
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[[Category: NESG, Northeast.Structural.Genomics.Consortium.]]
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[[Category: NESG, Northeast Structural Genomics Consortium.]]
[[Category: nesg]]
[[Category: nesg]]
[[Category: northeast structural genomics consortium]]
[[Category: northeast structural genomics consortium]]
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[[Category: structural genomics]]
[[Category: structural genomics]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:19:00 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:04:20 2008''

Revision as of 16:04, 21 February 2008


2jng

Drag the structure with the mouse to rotate

Solution structure of the CUL7-CPH domain from Homo Sapiens; Northeast Structural Genomics Consortium target HT1.

Contents

Overview

Cul7 is a member of the Cullin Ring Ligase (CRL) family and is required for normal mouse development and cellular proliferation. Recently, a region of Cul7 that is highly conserved in the p53-associated, Parkin-like cytoplasmic protein PARC, was shown to bind p53 directly. Here we identify the CPH domains (conserved domain within Cul7, PARC, and HERC2 proteins) of both Cul7 and PARC as p53 interaction domains using size exclusion chromatography and NMR spectroscopy. We present the first structure of the evolutionarily conserved CPH domain and provide novel insight into the Cul7-p53 interaction. The NMR structure of the Cul7-CPH domain reveals a fold similar to peptide interaction modules such as the SH3, Tudor, and KOW domains. The p53 interaction surface of both Cul7 and PARC CPH domains was mapped to a conserved surface distinct from the analogous peptide-binding regions of SH3, KOW, and Tudor domains, suggesting a novel mode of interaction. The CPH domain interaction surface of p53 resides in the tetramerization domain and is formed by residues contributed by at least two subunits.

Disease

Known disease associated with this structure: 3-M syndrome OMIM:[609577]

About this Structure

2JNG is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The conserved CPH domains of Cul7 and PARC are protein-protein interaction modules that bind the tetramerization domain of p53., Kaustov L, Lukin J, Lemak A, Duan S, Ho M, Doherty R, Penn LZ, Arrowsmith CH, J Biol Chem. 2007 Apr 13;282(15):11300-7. Epub 2007 Feb 12. PMID:17298945

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