PMID- 23221553 OWN - NLM STAT- MEDLINE DCOM- 20130322 LR - 20211021 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 87 IP - 4 DP - 2013 Feb TI - Betaretroviral envelope subunits are noncovalently associated and restricted to the mammalian class. PG - 1937-46 LID - 10.1128/JVI.01442-12 [doi] AB - The structure of the transmembrane subunit (TM) of the retroviral envelope glycoprotein (Env) is highly conserved among most retrovirus genera and includes a pair of cysteines that forms an intramolecular disulfide loop within the ectodomain. Alpha-, gamma-, and deltaretroviruses have a third cysteine, adjacent to the loop, which forms a disulfide bond between TM and the surface subunit (SU) of Env, while lentiviruses, which have noncovalently associated subunits, lack this third cysteine. The Betaretrovirus genus includes Jaagsiekte sheep retrovirus (JSRV) and mouse mammary tumor virus (MMTV), as well as many endogenous retroviruses. Envelope subunit association had not been characterized in the betaretroviruses, but lack of a third cysteine in the TM ectodomain suggested noncovalently associated subunits. We tested the Env proteins of JSRV and MMTV, as well as human endogenous retrovirus K (HERV-K)108--a betaretrovirus-like human endogenous retrovirus--for intersubunit bonding and found that, as in the lentiviruses, the Env subunits lack an intersubunit disulfide bond. Since these results suggest that the number of cysteines in the TM loop region readily distinguishes between covalent and noncovalent structure, we surveyed endogenous retroviral TM sequences in the genomes of vertebrates represented in public databases and found that (i) retroviruses with noncovalently associated subunits have been present during all of anthropoid evolution and (ii) the noncovalent env motif is limited to mammals, while the covalent type is found among five vertebrate classes. We discuss implications of these findings for retroviral evolution, cross-species transmissions, and recombination events involving the env gene. FAU - Henzy, Jamie E AU - Henzy JE AD - Tufts University School of Medicine, Department of Molecular Biology and Microbiology, Boston, Massachusetts, USA. FAU - Coffin, John M AU - Coffin JM LA - eng GR - R37 CA089441/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20121205 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Disulfides) RN - 0 (Protein Subunits) RN - 0 (Viral Envelope Proteins) RN - K848JZ4886 (Cysteine) SB - IM MH - Animals MH - Computational Biology MH - Cysteine/chemistry/genetics MH - Disulfides MH - Endogenous Retroviruses/*chemistry/genetics MH - Humans MH - Jaagsiekte sheep retrovirus/*chemistry/genetics MH - Mammary Tumor Virus, Mouse/*chemistry/genetics MH - Protein Binding MH - Protein Subunits/chemistry MH - Viral Envelope Proteins/*chemistry PMC - PMC3571459 EDAT- 2012/12/12 06:00 MHDA- 2013/03/23 06:00 PMCR- 2013/08/01 CRDT- 2012/12/11 06:00 PHST- 2012/12/11 06:00 [entrez] PHST- 2012/12/12 06:00 [pubmed] PHST- 2013/03/23 06:00 [medline] PHST- 2013/08/01 00:00 [pmc-release] AID - JVI.01442-12 [pii] AID - 01442-12 [pii] AID - 10.1128/JVI.01442-12 [doi] PST - ppublish SO - J Virol. 2013 Feb;87(4):1937-46. doi: 10.1128/JVI.01442-12. Epub 2012 Dec 5.