6K5T

Complex of SUMO1 and phosphorylated hcmv protein IE2

6K5T の概要

• エントリーDOI: 10.2210/pdb6k5t/pdb
• 分子名称: Small ubiquitin-related modifier 1, 12-mer from Viral transcription factor IE2 (2 entities in total)
• 機能のキーワード: complex, viral protein, protein binding-transcription complex, protein binding/transcription
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 10339.49

構造登録者

Tripathi, V.,Chatterjee, K.S. (登録日: 2019-05-31, 公開日: 2019-08-07, 最終更新日: 2024-10-09)

主引用文献

Tripathi, V.,Chatterjee, K.S.,Das, R.
Casein kinase-2-mediated phosphorylation increases the SUMO-dependent activity of the cytomegalovirus transactivator IE2.
J.Biol.Chem., 294:14546-14561, 2019

PubMed Abstract: Many viral factors manipulate the host post-translational modification (PTM) machinery for efficient viral replication. In particular, phosphorylation and SUMOylation can distinctly regulate the activity of the human cytomegalovirus (HCMV) transactivator immediate early 2 (IE2). However, the molecular mechanism of this process is unknown. Using various structural, biochemical, and cell-based approaches, here we uncovered that IE2 exploits a cross-talk between phosphorylation and SUMOylation. A scan for small ubiquitin-like modifier (SUMO)-interacting motifs (SIMs) revealed two SIMs in IE2, and a real-time SUMOylation assay indicated that the N-terminal SIM (IE2-SIM1) enhances IE2 SUMOylation up to 4-fold. Kinetic analysis and structural studies disclosed that IE2 is a SUMO E3 ligase. We also found that two putative casein kinase 2 (CK2) sites adjacent to IE2-SIM1 are phosphorylated and in cells. The phosphorylation drastically increased IE2-SUMO affinity, IE2 SUMOylation, and E3 activity of IE2. Additional salt bridges between the phosphoserines and SUMO accounted for the increased IE2-SUMO affinity. Phosphorylation also enhanced the SUMO-dependent transactivation activity and auto-repression activity of IE2. Together, our findings highlight a novel mechanism whereby SUMOylation and phosphorylation of the viral E3 ligase and transactivator protein IE2 work in tandem to enable transcriptional regulation of viral gene.

PubMed: 31371453
DOI: 10.1074/jbc.RA119.009601

実験手法

SOLUTION NMR