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

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

Research output: Contribution to journal › Article › peer-review

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. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Original language	English
Pages (from-to)	R661-R662
Number of pages	2
Journal	Current Biology
Volume	26
Issue number	14
Early online date	30 Jun 2016
DOIs	https://doi.org/10.1016/j.cub.2016.06.028
Publication status	Published - 25 Jul 2016

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10.1016/j.cub.2016.06.028

PIIS0960982216306674Final published version, 402 KBLicence: CC BY

http://linkinghub.elsevier.com/retrieve/pii/S0960982216306674

Cite this

@article{8f3e0657d9b24c55a20877c6781c6946,

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. Copyright {\textcopyright} 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.",

author = "Kaoru Nishimura and Ling Han and Enrica Bianchi and Wright, {Gavin J} and {de Sanctis}, Daniele and Luca Jovine",

year = "2016",

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doi = "10.1016/j.cub.2016.06.028",

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T1 - The structure of sperm Izumo1 reveals unexpected similarities with Plasmodium invasion proteins.

AU - Nishimura, Kaoru

AU - Han, Ling

AU - Bianchi, Enrica

AU - Wright, Gavin J

AU - de Sanctis, Daniele

AU - Jovine, Luca

PY - 2016/7/25

Y1 - 2016/7/25

N2 - 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. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

AB - 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. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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DO - 10.1016/j.cub.2016.06.028

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