5MF1

Crystal structure of a C-terminally truncated trimeric ectodomain of the Chlamydomonas reinhardtii gamete fusion protein HAP2

Summary for 5MF1

• Entry DOI: 10.2210/pdb5mf1/pdb
• Descriptor: Fusion protein HAP2/GCS1, 2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-galactopyranose (3 entities in total)
• Functional Keywords: class ii membrane fusion protein, type i transmembrane protein, glycoprotein, membrane protein
• Biological source: Chlamydomonas reinhardtii
• Cellular location: Cell membrane ; Single- pass type I membrane protein : A4GRC6
• Total number of polymer chains: 3
• Total formula weight: 194586.68

Authors

Fedry, J.,Rey, F.A.,Krey, T. (deposition date: 2016-11-17, release date: 2017-03-08, Last modification date: 2024-10-23)

Primary citation

Fedry, J.,Liu, Y.,Pehau-Arnaudet, G.,Pei, J.,Li, W.,Tortorici, M.A.,Traincard, F.,Meola, A.,Bricogne, G.,Grishin, N.V.,Snell, W.J.,Rey, F.A.,Krey, T.
The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein.
Cell, 168:904-915.e10, 2017

PubMed Abstract: Sexual reproduction is almost universal in eukaryotic life and involves the fusion of male and female haploid gametes into a diploid cell. The sperm-restricted single-pass transmembrane protein HAP2-GCS1 has been postulated to function in membrane merger. Its presence in the major eukaryotic taxa-animals, plants, and protists (including important human pathogens like Plasmodium)-suggests that many eukaryotic organisms share a common gamete fusion mechanism. Here, we report combined bioinformatic, biochemical, mutational, and X-ray crystallographic studies on the unicellular alga Chlamydomonas reinhardtii HAP2 that reveal homology to class II viral membrane fusion proteins. We further show that targeting the segment corresponding to the fusion loop by mutagenesis or by antibodies blocks gamete fusion. These results demonstrate that HAP2 is the gamete fusogen and suggest a mechanism of action akin to viral fusion, indicating a way to block Plasmodium transmission and highlighting the impact of virus-cell genetic exchanges on the evolution of eukaryotic life.

PubMed: 28235200
DOI: 10.1016/j.cell.2017.01.024

Experimental method

X-RAY DIFFRACTION (3.3 Å)