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 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.
Verfasserangaben: | Benjamin Stieglitz, Lesley F. Haire, Ivan ĐikićORCiDGND, Katrin Rittinger |
---|---|
URN: | urn:nbn:de:hebis:30:3-259336 |
URL: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375506/ |
DOI: | https://doi.org/10.1074/jbc.M112.359547 |
ISSN: | 1083-351X |
ISSN: | 0021-9258 |
Pubmed-Id: | https://pubmed.ncbi.nlm.nih.gov/22549881 |
Titel des übergeordneten Werkes (Englisch): | The journal of biological chemistry |
Verlag: | American Society for Biochemistry and Molecular Biology |
Verlagsort: | Bethesda, Md. |
Dokumentart: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Datum der Veröffentlichung (online): | 01.05.2012 |
Datum der Erstveröffentlichung: | 01.05.2012 |
Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Datum der Freischaltung: | 31.08.2012 |
Freies Schlagwort / Tag: | Protein Structure; Protein-Protein Interactions; Signal Transduction; Ubiquitin Ligase; Ubiquitination; X-ray Crystallography |
Jahrgang: | 287 |
Ausgabe / Heft: | 25 |
Seitenzahl: | 7 |
Erste Seite: | 20823 |
Letzte Seite: | 20829 |
Bemerkung: | © 2012 by The American Society for Biochemistry and Molecular Biology, Inc |
HeBIS-PPN: | 358061253 |
Institute: | Medizin / Medizin |
DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Sammlungen: | Universitätspublikationen |
Sammlung Biologie / Biologische Hochschulschriften (Goethe-Universität) | |
Lizenz (Deutsch): | Creative Commons - Namensnennung-Nicht kommerziell 3.0 |