6I4X

Crystal structure of SOCS2:Elongin C:Elongin B in complex with erythropoietin receptor peptide

6I4X の概要

• エントリーDOI: 10.2210/pdb6i4x/pdb
• 関連するPDBエントリー: 2C9W
• 分子名称: Elongin-B, Elongin-C, Suppressor of cytokine signaling 2, ... (6 entities in total)
• 機能のキーワード: complex, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 43459.43

構造登録者

Kung, W.W.,Ramachandran, S.,Makukhin, N.,Bruno, E.,Ciulli, A. (登録日: 2018-11-12, 公開日: 2019-05-29, 最終更新日: 2019-06-19)

主引用文献

Kung, W.W.,Ramachandran, S.,Makukhin, N.,Bruno, E.,Ciulli, A.
Structural insights into substrate recognition by the SOCS2 E3 ubiquitin ligase.
Nat Commun, 10:2534-2534, 2019

PubMed Abstract: The suppressor of cytokine signaling 2 (SOCS2) acts as substrate recognition subunit of a Cullin5 E3 ubiquitin ligase complex. SOCS2 binds to phosphotyrosine-modified epitopes as degrons for ubiquitination and proteasomal degradation, yet the molecular basis of substrate recognition has remained elusive. Here, we report co-crystal structures of SOCS2-ElonginB-ElonginC in complex with phosphorylated peptides from substrates growth hormone receptor (GHR-pY595) and erythropoietin receptor (EpoR-pY426) at 1.98 Å and 2.69 Å, respectively. Both peptides bind in an extended conformation recapitulating the canonical SH2 domain-pY pose, but capture different conformations of the EF loop via specific hydrophobic interactions. The flexible BG loop is fully defined in the electron density, and does not contact the substrate degron directly. Cancer-associated SNPs located around the pY pocket weaken substrate-binding affinity in biophysical assays. Our findings reveal insights into substrate recognition and specificity by SOCS2, and provide a blueprint for small molecule ligand design.

PubMed: 31182716
DOI: 10.1038/s41467-019-10190-4

実験手法

X-RAY DIFFRACTION (2.69 Å)