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Publication Abstract from PubMed

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.

Heme Oxygenase 2 Binds Myristate to Regulate Retrovirus Assembly and TLR4 Signaling.,Zhu Y, Luo S, Sabo Y, Wang C, Tong L, Goff SP Cell Host Microbe. 2017 Feb 8;21(2):220-230. doi: 10.1016/j.chom.2017.01.002., Epub 2017 Jan 26. PMID:28132836^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.