title: The structure of sperm Izumo1 reveals unexpected similarities with Plasmodium invasion proteins.
abstract: 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.
authors.affiliation: Department of Biosciences and Nutrition & Center for Innovative Medicine, Karolinska Institutet, Huddinge, SE-141 83, Sweden.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Department of Biosciences and Nutrition & Center for Innovative Medicine, Karolinska Institutet, Huddinge, SE-141 83, Sweden.
authors.forename: Ling
authors.initials: L
authors.lastname: Han
authors.affiliation: Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Enrica
authors.initials: E
authors.lastname: Bianchi
authors.affiliation: Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Wright
authors.affiliation: ESRF - The European Synchrotron, Grenoble 38000, France.
authors.forename: Daniele
authors.initials: D
authors.lastname: de Sanctis
authors.affiliation: Department of Biosciences and Nutrition & Center for Innovative Medicine, Karolinska Institutet, Huddinge, SE-141 83, Sweden. Electronic address: luca.jovine@ki.se.
authors.forename: Luca
authors.initials: L
authors.lastname: Jovine
mesh_terms: D000818:Animals; D007136:Immunoglobulins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051379:Mice / Q000235:genetics* / Q000378:metabolism; D010961:Plasmodium / Q000254:growth & development*; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics*; D020539:Sequence Analysis, Protein; D013094:Spermatozoa / Q000378:metabolism
chemical_list: D007136:Immunoglobulins; C498177:Izumo1 protein, mouse; D008565:Membrane Proteins; D015800:Protozoan Proteins