1ixd

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'''Solution structure of the CAP-GLY domain from human cylindromatosis tomour-suppressor CYLD'''<br />
'''Solution structure of the CAP-GLY domain from human cylindromatosis tomour-suppressor CYLD'''<br />
==Overview==
==Overview==
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CYLD was originally identified as the human familial cylindromatosis tumor, suppressor. Recently, it was reported that CYLD directly interacts with, NEMO/IKKgamma and TRAF2 in the NF-kappaB signaling pathway. The two, proteins bind to a region of CYLD that contains a Cys-box motif and the, third cytoskeleton-associated protein-glycine conserved (CAP-Gly) domain., Here we report that the third CAP-Gly domain of CYLD specifically, interacts with one of the two proline-rich sequences of NEMO/IKKgamma. The, tertiary structure of the CAP-Gly domain shares the five-stranded beta, sheet topology with the SH3 domain, which is well known as a proline-rich, sequence-recognition domain. However, chemical shift mapping revealed that, the peptide binding site of the CAP-Gly domain is formed without the long, peptide binding loop characteristic of the SH3 domain. Therefore, CAP-Gly, is likely to be a novel proline-rich sequence binding domain with a, mechanism different from that of the SH3 domain.
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CYLD was originally identified as the human familial cylindromatosis tumor suppressor. Recently, it was reported that CYLD directly interacts with NEMO/IKKgamma and TRAF2 in the NF-kappaB signaling pathway. The two proteins bind to a region of CYLD that contains a Cys-box motif and the third cytoskeleton-associated protein-glycine conserved (CAP-Gly) domain. Here we report that the third CAP-Gly domain of CYLD specifically interacts with one of the two proline-rich sequences of NEMO/IKKgamma. The tertiary structure of the CAP-Gly domain shares the five-stranded beta sheet topology with the SH3 domain, which is well known as a proline-rich sequence-recognition domain. However, chemical shift mapping revealed that the peptide binding site of the CAP-Gly domain is formed without the long peptide binding loop characteristic of the SH3 domain. Therefore, CAP-Gly is likely to be a novel proline-rich sequence binding domain with a mechanism different from that of the SH3 domain.
==Disease==
==Disease==
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==About this Structure==
==About this Structure==
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1IXD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Ubiquitin_thiolesterase Ubiquitin thiolesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.15 3.1.2.15] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1IXD OCA].
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1IXD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Ubiquitin_thiolesterase Ubiquitin thiolesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.15 3.1.2.15] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IXD OCA].
==Reference==
==Reference==
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[[Category: Kigawa, T.]]
[[Category: Kigawa, T.]]
[[Category: Koshiba, S.]]
[[Category: Koshiba, S.]]
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[[Category: RSGI, RIKEN.Structural.Genomics/Proteomics.Initiative.]]
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[[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]]
[[Category: Saito, K.]]
[[Category: Saito, K.]]
[[Category: Yokoyama, S.]]
[[Category: Yokoyama, S.]]
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[[Category: tumour suppressor]]
[[Category: tumour suppressor]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:35:43 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:16:48 2008''

Revision as of 11:16, 21 February 2008


1ixd

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Solution structure of the CAP-GLY domain from human cylindromatosis tomour-suppressor CYLD

Contents

Overview

CYLD was originally identified as the human familial cylindromatosis tumor suppressor. Recently, it was reported that CYLD directly interacts with NEMO/IKKgamma and TRAF2 in the NF-kappaB signaling pathway. The two proteins bind to a region of CYLD that contains a Cys-box motif and the third cytoskeleton-associated protein-glycine conserved (CAP-Gly) domain. Here we report that the third CAP-Gly domain of CYLD specifically interacts with one of the two proline-rich sequences of NEMO/IKKgamma. The tertiary structure of the CAP-Gly domain shares the five-stranded beta sheet topology with the SH3 domain, which is well known as a proline-rich sequence-recognition domain. However, chemical shift mapping revealed that the peptide binding site of the CAP-Gly domain is formed without the long peptide binding loop characteristic of the SH3 domain. Therefore, CAP-Gly is likely to be a novel proline-rich sequence binding domain with a mechanism different from that of the SH3 domain.

Disease

Known diseases associated with this structure: Cylindromatosis, familial OMIM:[605018]

About this Structure

1IXD is a Single protein structure of sequence from Homo sapiens. Active as Ubiquitin thiolesterase, with EC number 3.1.2.15 Full crystallographic information is available from OCA.

Reference

The CAP-Gly domain of CYLD associates with the proline-rich sequence in NEMO/IKKgamma., Saito K, Kigawa T, Koshiba S, Sato K, Matsuo Y, Sakamoto A, Takagi T, Shirouzu M, Yabuki T, Nunokawa E, Seki E, Matsuda T, Aoki M, Miyata Y, Hirakawa N, Inoue M, Terada T, Nagase T, Kikuno R, Nakayama M, Ohara O, Tanaka A, Yokoyama S, Structure. 2004 Sep;12(9):1719-28. PMID:15341735

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