5UC9

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

Summary for 5UC9

• Entry DOI: 10.2210/pdb5uc9/pdb
• Related: 5UC8 5UCA
• Descriptor: Heme oxygenase 2, MYRISTIC ACID (3 entities in total)
• Functional Keywords: heme oxygenase, myristic acid, oxidoreductase
• Biological source: Homo sapiens (Human)
• Cellular location: Microsome: P30519
• Total number of polymer chains: 4
• Total formula weight: 106060.04

Authors

Luo, S.,Tong, L. (deposition date: 2016-12-22, release date: 2017-02-15, Last modification date: 2023-10-04)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.903 Å)