Species-Specific Functional Regions of the Green Alga Gamete Fusion Protein HAP2 Revealed by Structural Studies

Structure. 2019 Jan 2;27(1):113-124.e4. doi: 10.1016/j.str.2018.09.014. Epub 2018 Nov 8.


The cellular fusion protein HAP2, which is structurally homologous to viral class II fusion proteins, drives gamete fusion across several eukaryotic kingdoms. Gamete fusion is a highly controlled process in eukaryotes, and is allowed only between same species gametes. In spite of a conserved architecture, HAP2 displays several species-specific functional regions that were not resolved in the available X-ray structure of the green alga Chlamydomonas reinhardtii HAP2 ectodomain. Here we present an X-ray structure resolving these regions, showing a target membrane interaction surface made by three amphipathic helices in a horseshoe-shaped arrangement. HAP2 from green algae also features additional species-specific motifs inserted in regions that in viral class II proteins are critical for the fusogenic conformational change. Such insertions include a cystine ladder-like module evocative of EGF-like motifs responsible for extracellular protein-protein interactions in animals, and a mucin-like region. These features suggest potential HAP2 interaction sites involved in gamete fusion control.

Keywords: Chlamydomonas reinhardtii; eukaryotic reproduction; fertilization; gamete fusion; green algae; last eukaryotic common ancestor; membrane fusion; protein evolution; structural biology; virus-cell gene exchanges in evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Chlamydomonas reinhardtii / chemistry
  • Chlamydomonas reinhardtii / metabolism*
  • Germ Cells / physiology
  • Membrane Proteins / chemistry*
  • Plant Proteins / chemistry*
  • Protein Domains


  • Membrane Proteins
  • Plant Proteins