2a9u
From Proteopedia
(New page: 200px<br /> <applet load="2a9u" size="450" color="white" frame="true" align="right" spinBox="true" caption="2a9u, resolution 2.10Å" /> '''Structure of the N-...) |
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caption="2a9u, resolution 2.10Å" /> | caption="2a9u, resolution 2.10Å" /> | ||
'''Structure of the N-terminal domain of Human Ubiquitin carboxyl-terminal hydrolase 8 (USP8)'''<br /> | '''Structure of the N-terminal domain of Human Ubiquitin carboxyl-terminal hydrolase 8 (USP8)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Ubiquitin-specific protease 8 (USP8) hydrolyzes mono and polyubiquitylated | + | Ubiquitin-specific protease 8 (USP8) hydrolyzes mono and polyubiquitylated targets such as epidermal growth factor receptors and is involved in clathrin-mediated internalization. In 1182 residues, USP8 contains multiple domains, including coiled-coil, rhodanese, and catalytic domains. We report the first high-resolution crystal structures of these domains and discuss their implications for USP8 function. The amino-terminal domain is a homodimer with a novel fold. It is composed of two five-helix bundles, where the first helices are swapped, and carboxyl-terminal helices are extended in an antiparallel fashion. The structure of the rhodanese domain, determined in complex with the E3 ligase NRDP1, reveals the canonical rhodanese fold but with a distorted primordial active site. The USP8 recognition domain of NRDP1 has a novel protein fold that interacts with a conserved peptide loop of the rhodanese domain. A consensus sequence of this loop is found in other NRDP1 targets, suggesting a common mode of interaction. The structure of the carboxyl-terminal catalytic domain of USP8 exhibits the conserved tripartite architecture but shows unique traits. Notably, the active site, including the ubiquitin binding pocket, is in a closed conformation, incompatible with substrate binding. The presence of a zinc ribbon subdomain near the ubiquitin binding site further suggests a polyubiquitin-specific binding site and a mechanism for substrate induced conformational changes. |
==About this Structure== | ==About this Structure== | ||
| - | 2A9U 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:// | + | 2A9U 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=2A9U OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Ubiquitin thiolesterase]] | [[Category: Ubiquitin thiolesterase]] | ||
[[Category: Arrowsmith, C.]] | [[Category: Arrowsmith, C.]] | ||
| - | [[Category: Avvakumov, G | + | [[Category: Avvakumov, G V.]] |
[[Category: Bochkarev, A.]] | [[Category: Bochkarev, A.]] | ||
[[Category: Dhe-Paganon, S.]] | [[Category: Dhe-Paganon, S.]] | ||
[[Category: Edwards, E.]] | [[Category: Edwards, E.]] | ||
[[Category: Mackenzie, F.]] | [[Category: Mackenzie, F.]] | ||
| - | [[Category: Newman, E | + | [[Category: Newman, E M.]] |
| - | [[Category: SGC, Structural | + | [[Category: SGC, Structural Genomics Consortium.]] |
[[Category: Sundstrom, M.]] | [[Category: Sundstrom, M.]] | ||
| - | [[Category: Walker, J | + | [[Category: Walker, J R.]] |
[[Category: Weigelt, J.]] | [[Category: Weigelt, J.]] | ||
[[Category: Xue, S.]] | [[Category: Xue, S.]] | ||
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[[Category: ubl conjugation pathway]] | [[Category: ubl conjugation pathway]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:25:17 2008'' |
Revision as of 14:25, 21 February 2008
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Structure of the N-terminal domain of Human Ubiquitin carboxyl-terminal hydrolase 8 (USP8)
Overview
Ubiquitin-specific protease 8 (USP8) hydrolyzes mono and polyubiquitylated targets such as epidermal growth factor receptors and is involved in clathrin-mediated internalization. In 1182 residues, USP8 contains multiple domains, including coiled-coil, rhodanese, and catalytic domains. We report the first high-resolution crystal structures of these domains and discuss their implications for USP8 function. The amino-terminal domain is a homodimer with a novel fold. It is composed of two five-helix bundles, where the first helices are swapped, and carboxyl-terminal helices are extended in an antiparallel fashion. The structure of the rhodanese domain, determined in complex with the E3 ligase NRDP1, reveals the canonical rhodanese fold but with a distorted primordial active site. The USP8 recognition domain of NRDP1 has a novel protein fold that interacts with a conserved peptide loop of the rhodanese domain. A consensus sequence of this loop is found in other NRDP1 targets, suggesting a common mode of interaction. The structure of the carboxyl-terminal catalytic domain of USP8 exhibits the conserved tripartite architecture but shows unique traits. Notably, the active site, including the ubiquitin binding pocket, is in a closed conformation, incompatible with substrate binding. The presence of a zinc ribbon subdomain near the ubiquitin binding site further suggests a polyubiquitin-specific binding site and a mechanism for substrate induced conformational changes.
About this Structure
2A9U 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
Amino-terminal dimerization, NRDP1-rhodanese interaction, and inhibited catalytic domain conformation of the ubiquitin-specific protease 8 (USP8)., Avvakumov GV, Walker JR, Xue S, Finerty PJ Jr, Mackenzie F, Newman EM, Dhe-Paganon S, J Biol Chem. 2006 Dec 8;281(49):38061-70. Epub 2006 Oct 11. PMID:17035239
Page seeded by OCA on Thu Feb 21 16:25:17 2008
Categories: Homo sapiens | Single protein | Ubiquitin thiolesterase | Arrowsmith, C. | Avvakumov, G V. | Bochkarev, A. | Dhe-Paganon, S. | Edwards, E. | Mackenzie, F. | Newman, E M. | SGC, Structural Genomics Consortium. | Sundstrom, M. | Walker, J R. | Weigelt, J. | Xue, S. | Coil-coil | Hydrolase | Protease | Sgc | Sh3-binding | Structural genomics | Structural genomics consortium | Thiol protease | Ubl conjugation pathway
