Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains

被引：272

作者：

Sato, Yusuke ^{[1
,2
,3
]}

Yoshikawa, Azusa ^{[1
,2
,3
]}

Yamagata, Atsushi ^{[1
,2
]}

Mimura, Hisatoshi ^{[1
,2
]}

Yamashita, Masami ^{[1
,2
,5
]}

Ookata, Kayoko ^{[3
]}

Nureki, Osamu ^{[3
]}

Iwai, Kazuhiro ^{[6
]}

Komada, Masayuki ^{[4
]}

Fukai, Shuya ^{[1
,2
,5
]}

机构：

[1] Univ Tokyo, Struct Biol Lab, Div Life Sci, Synchrotron Radiat Res Org, Tokyo 1130032, Japan

[2] Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo 1130032, Japan

[3] Tokyo Inst Technol, Dept Biol Informat, Yokohama, Kanagawa 2268501, Japan

[4] Tokyo Inst Technol, Dept Biol Sci, Grad Sch Biosci & Biotechnol, Yokohama, Kanagawa 2268501, Japan

[5] Univ Tokyo, Dept Med Genome Sci, Grad Sch Frontier Sci, Chiba 2778501, Japan

[6] Osaka Univ, Dept Biophys & Biochem, Grad Sch Med, Suita, Osaka 5650871, Japan

来源：

NATURE | 2008年 / 455卷 / 7211期

关键词：

D O I：

10.1038/nature07254

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Deubiquitinating enzymes ( DUBs) remove ubiquitin from conjugated substrates to regulate various cellular processes. The Zn2+-dependent DUBs AMSH and AMSH- LP regulate receptor trafficking by specifically cleaving Lys 63- linked polyubiquitin chains from internalized receptors. Here we report the crystal structures of the human AMSH- LP DUB domain alone and in complex with a Lys 63- linked di- ubiquitin at 1.2 angstrom and 1.6 angstrom resolutions, respectively. The AMSH- LP DUB domain consists of a Zn2+-coordinating catalytic core and two characteristic insertions, Ins- 1 and Ins- 2. The distal ubiquitin interacts with Ins- 1 and the core, whereas the proximal ubiquitin interacts with Ins- 2 and the core. The core and Ins- 1 form a catalytic groove that accommodates the Lys 63 side chain of the proximal ubiquitin and the isopeptide- linked carboxy- terminal tail of the distal ubiquitin. This is the first reported structure of a DUB in complex with an isopeptide- linked ubiquitin chain, which reveals the mechanism for Lys 63- linkage- specific deubiquitination by AMSH family members.

引用

页码：358 / U19

页数：6

共 49 条

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