2IZV

CRYSTAL STRUCTURE OF SOCS-4 IN COMPLEX WITH ELONGIN-B AND ELONGIN-C AT 2.55A RESOLUTION

2IZV の概要

• エントリーDOI: 10.2210/pdb2izv/pdb
• 関連するPDBエントリー: 1LM8 1LQB 1VCB 2C9W
• 分子名称: SUPPRESSOR OF CYTOKINE SIGNALING 4, TRANSCRIPTION ELONGATION FACTOR B POLYPEPTIDE 2, TRANSCRIPTION ELONGATION FACTOR B POLYPEPTIDE 1, ... (7 entities in total)
• 機能のキーワード: signal transduction inhibitor, growth regulation, signal transduction, sh2 domain, transcription, nuclear protein, ubl conjugation pathway, transcription regulation
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 45979.62

構造登録者

Debreczeni, J.E.,Bullock, A.,Papagrigoriou, E.,Turnbull, A.,Pike, A.C.W.,Gorrec, F.,von Delft, F.,Sundstrom, M.,Arrowsmith, C.,Weigelt, J.,Edwards, A.,Knapp, S. (登録日: 2006-07-26, 公開日: 2006-08-02, 最終更新日: 2023-12-13)

主引用文献

Bullock, A.N.,Rodriguez, M.C.,Debreczeni, J.E.,Songyang, Z.,Knapp, S.
Structure of the SOCS4-ElonginB/C complex reveals a distinct SOCS box interface and the molecular basis for SOCS-dependent EGFR degradation.
Structure, 15:1493-1504, 2007

PubMed Abstract: Tyrosine kinase signaling is tightly controlled by negative feedback inhibitors including suppressors of cytokine signaling (SOCS). SOCS assemble as SH2 domain substrate recognition modules in ElonginB/C-cullin ubiquitin ligases. In accordance, SOCS4 reduces STAT3 signaling from EGFR through increased receptor degradation. Variable C-termini in SOCS4-SOCS7 exclude these family members from a SOCS2-type domain arrangement in which a strictly conserved C terminus determines domain packing. The structure of the SOCS4-ElonginC-ElonginB complex reveals a distinct SOCS structural class. The N-terminal ESS helix functionally replaces the CIS/SOCS1-SOCS3 family C terminus in a distinct SH2-SOCS box interface that facilitates further interdomain packing between the extended N- and C-terminal regions characteristic for this subfamily. Using peptide arrays and calorimetry the STAT3 site in EGFR (pY(1092)) was identified as a high affinity SOCS4 substrate (K(D) = 0.5 microM) revealing a mechanism for EGFR degradation. SOCS4 also bound JAK2 and KIT with low micromolar affinity, whereas SOCS2 was specific for GH-receptor.

PubMed: 17997974
DOI: 10.1016/j.str.2007.09.016

実験手法

X-RAY DIFFRACTION (2.55 Å)