5BO4

Structure of SOCS2:Elongin C:Elongin B from DMSO-treated crystals

5BO4 の概要

• エントリーDOI: 10.2210/pdb5bo4/pdb
• 分子名称: Suppressor of cytokine signaling 2, Transcription elongation factor B polypeptide 2, Transcription elongation factor B polypeptide 1, ... (4 entities in total)
• 機能のキーワード: signaling protein, ubiquitin ligase, suppressor of cytokine signalling
• 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: 18
• 化学式量合計: 253225.53

構造登録者

Gadd, M.S.,Bulatov, E.,Ciulli, A. (登録日: 2015-05-27, 公開日: 2015-07-08, 最終更新日: 2024-10-09)

主引用文献

Gadd, M.S.,Bulatov, E.,Ciulli, A.
Serendipitous SAD Solution for DMSO-Soaked SOCS2-ElonginC-ElonginB Crystals Using Covalently Incorporated Dimethylarsenic: Insights into Substrate Receptor Conformational Flexibility in Cullin RING Ligases.
Plos One, 10:e0131218-e0131218, 2015

PubMed Abstract: Suppressor of cytokine signalling 2 (SOCS2) is the substrate-binding component of a Cullin-RING E3 ubiquitin ligase (CRL) complex that targets phosphorylated hormone receptors for degradation by the ubiquitin-proteasome system. As a key regulator of the transcriptional response to growth signals, SOCS2 and its protein complex partners are potential targets for small molecule development. We found that crystals of SOCS2 in complex with its adaptor proteins, Elongin C and Elongin B, underwent a change in crystallographic parameters when treated with dimethyl sulfoxide during soaking experiments. To solve the phase problem for the new crystal form we identified the presence of arsenic atoms in the crystals, a result of covalent modification of cysteines by cacodylate, and successfully extracted anomalous signal from these atoms for experimental phasing. The resulting structure provides a means for solving future structures where the crystals must be treated with DMSO for ligand soaking approaches. Additionally, the conformational changes induced in this structure reveal flexibility within SOCS2 that match those postulated by previous molecular dynamics simulations. This conformational flexibility illustrates how SOCS2 can orient its substrates for successful ubiquitination by other elements of the CRL complex.

PubMed: 26121586
DOI: 10.1371/journal.pone.0131218

実験手法

X-RAY DIFFRACTION (2.9 Å)