4EMO

Crystal structure of the PH domain of SHARPIN

4EMO の概要

• エントリーDOI: 10.2210/pdb4emo/pdb
• 分子名称: Sharpin (2 entities in total)
• 機能のキーワード: pleckstrin homology (ph) domain, lubac, sipl1, linear ubiquitin, hoil-1l, hoip, protein binding
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytosol: Q9H0F6
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 53422.10

構造登録者

Stieglitz, B.,Haire, L.F.,Dikic, I.,Rittinger, K. (登録日: 2012-04-12, 公開日: 2012-05-02, 最終更新日: 2024-11-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2 Å)