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

Kaoru Nishimura,Ling Han,Enrica Bianchi,Gavin J Wright,Daniele De Sanctis,Luca Jovine

doi:10.1016/j.cub.2016.06.028

Abstract

SummaryFertilization, 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.

Highlights

Fertilization, the culminating event in sexual reproduction, occurs when haploid sperm and egg recognize each other and fuse to form a diploid zygote
The biological activity of Izumo1 depends on the amino-terminal half of its ectodomain — a region named the ‘Izumo domain’ because it is shared with the paralogous sperm proteins Izumo2, 3 and 4 [6]; this region is followed by a glycosylated Ig-like domain [2] (Figure 1A)
These features result in an elongated architecture stabilized by five intramolecular disulfide bonds that are conserved in the three Izumo paralogs, and are clearly discernible within the sequence of Spaca6, another sperm surface protein recently reported to be required for gamete fusion [7] (Figure S2A,B)

Summary

Introduction

Fertilization, the culminating event in sexual reproduction, occurs when haploid sperm and egg recognize each other and fuse to form a diploid zygote. The biological activity of Izumo1 depends on the amino-terminal half of its ectodomain — a region named the ‘Izumo domain’ because it is shared with the paralogous sperm proteins Izumo2, 3 and 4 [6]; this region is followed by a glycosylated Ig-like domain [2] (Figure 1A).

Results

Conclusion