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The crystal structure of the catalytic domain of the endosome‐associated deubiquitinating enzyme, AMSH
Author(s) -
Davies Christopher W,
Paul Lake,
Das Chittaranjan
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.711.1
Subject(s) - deubiquitinating enzyme , endosome , ubiquitin , domain (mathematical analysis) , chemistry , enzyme , microbiology and biotechnology , biology , biochemistry , receptor , mathematical analysis , mathematics , gene
The endosomal‐sorting complex required for transport (ESCRT) is a ubiquitin‐dependent machinery that is used for internalization of cell surface receptors. The ESCRT complex facilitates the invagination of early endosomes containing ubiquitinated cargo destined for degradation. Two deubiquitinating enzymes (DUBs) regulate the activity of the ESCRT complex, associated molecule with a Src homology 3 domain (AMSH), and ubiquitin specific protease 8 (USP8/UBPY), by counteracting the ubiquitination of the cargo and/or the ESCRT members themselves. We have crystallized and determined the structure of the catalytic domain of AMSH to 2.5Å resolution. The structure of the catalytic domain is similar to the catalytic domain of the previously determined AMSH‐like protein (AMSH‐LP); however, based on the observation that AMSH, not AMSH‐LP, is used in the ESCRT‐mediated receptor down‐regulation, we propose that there maybe significant biochemical differences between the two proteins even though they have similar structures of their catalytic domain, a hypothesis we are investigating using mutational analysis. Results from our studies could help in understanding the role of AMSH within the ESCRT complex.