5UC9

Crystal structure of human Heme Oxygenase-2 in complex with Myristate

5UC9 の概要

• エントリーDOI: 10.2210/pdb5uc9/pdb
• 関連するPDBエントリー: 5UC8 5UCA
• 分子名称: Heme oxygenase 2, MYRISTIC ACID (3 entities in total)
• 機能のキーワード: heme oxygenase, myristic acid, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Microsome: P30519
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 106060.04

構造登録者

Luo, S.,Tong, L. (登録日: 2016-12-22, 公開日: 2017-02-15, 最終更新日: 2023-10-04)

主引用文献

Zhu, Y.,Luo, S.,Sabo, Y.,Wang, C.,Tong, L.,Goff, S.P.
Heme Oxygenase 2 Binds Myristate to Regulate Retrovirus Assembly and TLR4 Signaling.
Cell Host Microbe, 21:220-230, 2017

PubMed Abstract: N-myristoylation is the covalent attachment of myristic acid to the N terminus of proteins in eukaryotic cells. The matrix domain (MA) of HIV-1 Gag protein is N-myristoylated and plays an important role in virus budding. In screening for host factors that interact with HIV-1 MA, we found that heme oxygenase (HO-2) specifically binds the myristate moiety of Gag. HO-2 was also found to bind TRAM, an adaptor protein for Toll-like receptor 4 (TLR4), and thereby impact both virus replication and cellular inflammatory responses. A crystal structure revealed that HO-2 binds myristate via a hydrophobic channel adjacent to the heme-binding pocket. Inhibiting HO-2 expression, or blocking myristate binding with a heme analog, led to marked increases in virus production. HO-2 deficiency caused hyperresponsive TRAM-dependent TLR4 signaling and hypersensitivity to the TLR4 ligand lipopolysaccharide. Thus, HO-2 is a cellular myristate-binding protein that negatively regulates both virus replication and host inflammatory responses.

PubMed: 28132836
DOI: 10.1016/j.chom.2017.01.002

実験手法

X-RAY DIFFRACTION (1.903 Å)