The structure of sperm Izumo1 reveals unexpected similarities with Plasmodium invasion proteins

Curr Biol. 2016 Jul 25;26(14):R661-2. doi: 10.1016/j.cub.2016.06.028. Epub 2016 Jun 30.


Fertilization, the culminating event in sexual reproduction, occurs when haploid sperm and egg recognize each other and fuse to form a diploid zygote. In mammals this process critically depends on the interaction between Izumo1, a protein exposed on the equatorial segment of acrosome-reacted sperm, and the egg plasma-membrane-anchored receptor Juno [1,2]. The molecular mechanism triggering gamete fusion is unresolved because both Izumo1 and Juno lack sequence similarity to known membrane fusogens. Here we report the crystal structure of Izumo1, which reveals a membrane distal region composed of a four-helix bundle connected to a carboxy-terminal immunoglobulin (Ig)-like domain through a β-hairpin stabilized by disulfide bonds. Remarkably, different regions of Izumo1 display significant structural similarities to two proteins expressed by the invasive sporozoite stage of Plasmodium parasites: SPECT1, which is essential for host cell traversal and hepatocyte invasion [3]; and TRAP, which is necessary for gliding motility and invasion [4]. These observations suggest a link between the molecular mechanisms underlying host cell invasion by the malaria parasite and gamete membrane fusion at fertilization.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Immunoglobulins / chemistry
  • Immunoglobulins / genetics*
  • Immunoglobulins / metabolism
  • Male
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice / genetics*
  • Mice / metabolism
  • Plasmodium / growth & development*
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics*
  • Sequence Analysis, Protein
  • Spermatozoa / metabolism


  • Immunoglobulins
  • Izumo1 protein, mouse
  • Membrane Proteins
  • Protozoan Proteins