4EMO

Crystal structure of the PH domain of SHARPIN

Summary for 4EMO

• Entry DOI: 10.2210/pdb4emo/pdb
• Descriptor: Sharpin (2 entities in total)
• Functional Keywords: pleckstrin homology (ph) domain, lubac, sipl1, linear ubiquitin, hoil-1l, hoip, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytosol: Q9H0F6
• Total number of polymer chains: 4
• Total formula weight: 53422.10

Authors

Stieglitz, B.,Haire, L.F.,Dikic, I.,Rittinger, K. (deposition date: 2012-04-12, release date: 2012-05-02, Last modification date: 2024-11-27)

Primary citation

Stieglitz, B.,Haire, L.F.,Dikic, I.,Rittinger, K.
Structural Analysis of SHARPIN, a Subunit of a Large Multi-protein E3 Ubiquitin Ligase, Reveals a Novel Dimerization Function for the Pleckstrin Homology Superfold.
J.Biol.Chem., 287:20823-20829, 2012

PubMed 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.

PubMed: 22549881
DOI: 10.1074/jbc.M112.359547

Experimental method

X-RAY DIFFRACTION (2 Å)