TY  - JOUR
A1  - Stieglitz, Benjamin
A1  - Haire, Lesley F.
A1  - Đikić, Ivan
A1  - Rittinger, Katrin
T1  - Structural analysis of SHARPIN, a subunit of a large multi-protein E3 ubiquitin ligase, reveals a novel dimerization function for the pleckstrin homology superfold
T2  - The journal of biological chemistry
N2  - 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.
KW  - Protein Structure
KW  - Protein-Protein Interactions
KW  - Signal Transduction
KW  - Ubiquitin Ligase
KW  - Ubiquitination
KW  - X-ray Crystallography
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/25933
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-259336
UR  - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375506/
SN  - 1083-351X
SN  - 0021-9258
N1  - © 2012 by The American Society for Biochemistry and Molecular Biology, Inc
VL  - 287
IS  - 25
SP  - 20823
EP  - 20829
PB  - American Society for Biochemistry and Molecular Biology
CY  - Bethesda, Md.
ER  -