Structural analysis of SHARPIN, a subunit of a large multi-protein E3 ubiquitin ligase, reveals a novel dimerization function for the pleckstrin homology superfold

SHARPIN (SHANK-associated RH domain interacting protein) is part of a large multi-protein E3 ubiquitin ligase complex called LUBAC (linear ubiquitin chain assembly complex), which catalyzes the formation of linear ubiqui
SHARPIN (SHANK-associated RH domain interacting protein) is part of a large multi-protein E3 ubiquitin ligase complex called LUBAC (linear ubiquitin chain assembly complex), which catalyzes the formation of linear ubiquitin chains and regulates immune and apoptopic signaling pathways. The C-terminal half of SHARPIN contains ubiquitin-like domain and Npl4-zinc finger domains that mediate the interaction with the LUBAC subunit HOIP and ubiquitin, respectively. In contrast, the N-terminal region does not show any homology with known protein interaction domains but has been suggested to be responsible for self-association of SHARPIN, presumably via a coiled-coil region. We have determined the crystal structure of the N-terminal portion of SHARPIN, which adopts the highly conserved pleckstrin homology superfold that is often used as a scaffold to create protein interaction modules. We show that in SHARPIN, this domain does not appear to be used as a ligand recognition domain because it lacks many of the surface properties that are present in other pleckstrin homology fold-based interaction modules. Instead, it acts as a dimerization module extending the functional applications of this superfold.
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Metadaten
Author:Benjamin Stieglitz, Lesley F. Haire, Ivan Dikic, Katrin Rittinger
URN:urn:nbn:de:hebis:30:3-259336
URL:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375506/
DOI:http://dx.doi.org/10.1074/jbc.M112.359547
ISSN:1083-351X
ISSN:0021-9258
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=22549881
Parent Title (English):The journal of biological chemistry
Publisher:American Society for Biochemistry and Molecular Biology
Place of publication:Bethesda, Md.
Document Type:Article
Language:English
Date of Publication (online):2012/05/01
Date of first Publication:2012/05/01
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2012/08/31
Tag:Protein Structure; Protein-Protein Interactions; Signal Transduction; Ubiquitin Ligase; Ubiquitination; X-ray Crystallography
Volume:287
Issue:25
Pagenumber:7
First Page:20823
Last Page:20829
Note:
© 2012 by The American Society for Biochemistry and Molecular Biology, Inc
HeBIS PPN:358061253
Institutes:Medizin
Dewey Decimal Classification:570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Biologische Hochschulschriften (Goethe-Universität)
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 3.0

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