6C5X

Crystal Structure of SOCS1 in complex with ElonginB and ElonginC

6C5X の概要

• エントリーDOI: 10.2210/pdb6c5x/pdb
• 分子名称: Elongin-B, Elongin-C, Suppressor of Cytokine Signalling 1, ... (5 entities in total)
• 機能のキーワード: complex, ubiquitination, cytokine signalling, socs, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus : Q15370 Q15369
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 87127.09

構造登録者

Kershaw, N.J.,Laktyushin, A.,Babon, J.J. (登録日: 2018-01-17, 公開日: 2018-05-02, 最終更新日: 2024-10-23)

主引用文献

Liau, N.P.D.,Laktyushin, A.,Lucet, I.S.,Murphy, J.M.,Yao, S.,Whitlock, E.,Callaghan, K.,Nicola, N.A.,Kershaw, N.J.,Babon, J.J.
The molecular basis of JAK/STAT inhibition by SOCS1.
Nat Commun, 9:1558-1558, 2018

PubMed Abstract: The SOCS family of proteins are negative-feedback inhibitors of signalling induced by cytokines that act via the JAK/STAT pathway. SOCS proteins can act as ubiquitin ligases by recruiting Cullin5 to ubiquitinate signalling components; however, SOCS1, the most potent member of the family, can also inhibit JAK directly. Here we determine the structural basis of both these modes of inhibition. Due to alterations within the SOCS box domain, SOCS1 has a compromised ability to recruit Cullin5; however, it is a direct, potent and selective inhibitor of JAK catalytic activity. The kinase inhibitory region of SOCS1 targets the substrate binding groove of JAK with high specificity and thereby blocks any subsequent phosphorylation. SOCS1 is a potent inhibitor of the interferon gamma (IFNγ) pathway, however, it does not bind the IFNγ receptor, making its mode-of-action distinct from SOCS3. These findings reveal the mechanism used by SOCS1 to inhibit signalling by inflammatory cytokines.

PubMed: 29674694
DOI: 10.1038/s41467-018-04013-1

実験手法

X-RAY DIFFRACTION (3.105 Å)