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Structural analysis of SHARPIN, a subunit of a large multi-protein E3 ubiquitin ligase, reveals a novel dimerization function for the pleckstrin homology superfold.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2012 Jun 15; Vol. 287 (25), pp. 20823-9. Date of Electronic Publication: 2012 May 01. - Publication Year :
- 2012
-
Abstract
- 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.
- Subjects :
- Blood Proteins chemistry
Crystallography, X-Ray
Humans
Phosphoproteins chemistry
Protein Structure, Quaternary
Protein Structure, Tertiary
Structure-Activity Relationship
Zinc Fingers
Nerve Tissue Proteins chemistry
Protein Folding
Protein Multimerization
Protein Subunits chemistry
Ubiquitin-Protein Ligases chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 287
- Issue :
- 25
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 22549881
- Full Text :
- https://doi.org/10.1074/jbc.M112.359547