title: Crystal structure of a pivotal domain of human syncytin-2, a 40 million years old endogenous retrovirus fusogenic envelope gene captured by primates.
abstract: HERV-FRD is a human endogenous retrovirus that entered the human genome 40 million years ago. Its envelope gene, syncytin-2, was diverted by an ancestral host most probably because of its fusogenic property, for a role in placenta morphogenesis. It was maintained in a functional state in all primate branches as a bona fide cellular gene, submitted to a very low mutation rate as compared to infectious retrovirus genomes. The structure of the syncytin-2 protein thus provides a good insight into that of the oldest mammalian retroviral envelope. Here, we report the crystal structure of a central fragment of its "fossil" ectodomain, allowing a remarkable superposition with the structures of the corresponding domains of present-day infectious retroviruses, in spite of a more than 60% divergent sequence. These results suggest the existence of a unique structural solution selected by these proteins for their fusogenic function.
authors.affiliation: Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs, UMR 8122 CNRS, Institut Gustave Roussy, 94805 Villejuif, France.
authors.forename: Martial
authors.initials: M
authors.lastname: Renard
authors.forename: Paloma F
authors.initials: PF
authors.lastname: Varela
authors.forename: Claire
authors.initials: C
authors.lastname: Letzelter
authors.forename: Stéphane
authors.initials: S
authors.lastname: Duquerroy
authors.forename: Félix A
authors.initials: FA
authors.lastname: Rey
authors.forename: Thierry
authors.initials: T
authors.lastname: Heidmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002459:Cell Fusion; D018360:Crystallography, X-Ray; D015686:Gene Products, env / Q000737:chemistry* / Q000502:physiology; D015368:Human T-lymphotropic virus 1 / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000737:chemistry; D011257:Pregnancy Proteins / Q000737:chemistry* / Q000502:physiology; D011323:Primates / Q000821:virology*; D017434:Protein Structure, Tertiary; D012190:Retroviridae / Q000737:chemistry / Q000235:genetics*; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D015686:Gene Products, env; D011257:Pregnancy Proteins; D014764:Viral Proteins; C405335:syncytin