2ZNR

Crystal structure of the DUB domain of human AMSH-LP

Summary for 2ZNR

• Entry DOI: 10.2210/pdb2znr/pdb
• Related: 2ZNV
• Descriptor: AMSH-like protease, ZINC ION, PRASEODYMIUM ION, ... (5 entities in total)
• Functional Keywords: metal binding protein, alternative splicing, hydrolase, metal-binding, metalloprotease, protease, ubl conjugation pathway, zinc
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 20680.47

Authors

Sato, Y.,Azusa, Y.,Yamagata, A.,Mimura, H.,Wang, X.,Yamashita, M.,Ookata, K.,Nureki, O.,Iwai, K.,Komada, M.,Fukai, S. (deposition date: 2008-05-01, release date: 2008-09-02, Last modification date: 2024-03-13)

Primary citation

Sato, Y.,Yoshikawa, A.,Yamagata, A.,Mimura, H.,Yamashita, M.,Ookata, K.,Nureki, O.,Iwai, K.,Komada, M.,Fukai, S.
Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains
Nature, 455:358-362, 2008

PubMed Abstract: Deubiquitinating enzymes (DUBs) remove ubiquitin from conjugated substrates to regulate various cellular processes. The Zn(2+)-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 A and 1.6 A resolutions, respectively. The AMSH-LP DUB domain consists of a Zn(2+)-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.

PubMed: 18758443
DOI: 10.1038/nature07254

Experimental method

X-RAY DIFFRACTION (1.2 Å)