Читать книгу Principles of Virology - Jane Flint, S. Jane Flint - Страница 239

Gamete adhesion and fusion. Chlamydomonas gamete fusion is used as an example. Cilia on the gamete surface adhere to each other, bringing the two gametes together and activating the formation of mating structures on each gamete. The mating structures bind to each other via cell-specific adhesion proteins, and the HAP2 protein mediates membrane fusion between the two cells. (Inset) Models of the hairpin conformation of HAP2 proteins based on viral class II fusion proteins and structure of Chlamydomonas HAP2 trimer (PDB ID: 6DBS). Monomers are colored gray, yellow, or multiple colors to match Fig. 5.18.

Sex distinguishes eukaryotes from other organisms. Meiotic division produces two haploid germ cells, gametes, that must subsequently meet and merge to produce a cell with a new diploid genome. The processes of “meeting and merging” are poorly understood but are analogous to those of viral surface proteins binding to and fusing with their specific target cells.

Insight into the gamete fusion process came from the identification and subsequent structural studies of proteins from the plants Arabidopsis thaliana and Lilium longiflorum. The protein was named HAP2 (for hapless) because mutant Arabidopsis plants lacking it did not produce fertile male gametes. Orthologues of HAP2 were subsequently discovered in the parasite Plasmodium falciparum, the green alga Chlamydomonas reinhardtii, the invertebrate animals Hydra and Apis (honeybee), and additional eukaryotic species.

The function of these proteins was not obvious, for their primary amino acid sequence did not resemble that of any other protein. However, X-ray crystallography revealed that HAP2 can adopt a trimeric structure that resembles that of class II viral fusion proteins in the fusion active state (see Fig. 5.18). Like the hairpin conformation of the viral fusion proteins, the HAP2 domain II (cyan) that contains the fusion loops (red) is extended toward the target membrane, while domain III (black) is folded against domain I (orange) to bring the membranes of the fusion partners into close proximity.

Several questions remain: What mediates specific attachment of gametes to each other? What is the fusion trigger? What protein fulfills this function in other eukaryotes, including mammals? And how did it arise? Given that HAP2 is ancient, presumably emerging at the same time as sexual reproduction, one possibility is that it was coopted from viruses reproducing in the precursors of sex cells. HAP2 would not be the only example of a viral fusion protein diverted by the host organism. Syncytins, proteins that are critical for the development of the placenta, are related to retroviral class I fusion proteins and were acquired independently in several mammalian lineages. For all the harm that viruses impart on their various host species, it appears that life as we know it might be quite different without them. Sex, for one thing, might be absent.

 Fédry J, Liu Y, Péhau-Arnaudet G, Pei J, Li W, Tortorici MA, Traincard F, Meola A, Bricogne G, Grishin NV, Snell WJ, Rey FA, Krey T. 2017. The ancient gamete fusogen HAP2 is a eukaryotic class II fusion protein. Cell 168:904–915.e10.

 Feng J, Dong X, Pinello J, Zhang J, Lu C, Iacob RE, Engen JR, Snell WJ, Springer TA. 2018. Fusion surface structure, function, and dynamics of gamete fusogen HAP2. eLife 7:397772.