PDBsum entry 5jk9

Cell adhesion

PDB id: 5jk9

Contents

Protein chains

241 a.a.

212 a.a.

Ligands

NAG ×6

Waters ×537

PDB id:

5jk9

Name:

Cell adhesion

Title:

Crystal structure of human izumo1

Structure:

Izumo sperm-egg fusion protein 1. Chain: a, b, c, d, e, f. Fragment: unp residues 22-255. Synonym: oocyte binding/fusion factor,obf,sperm-specific protein izumo. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: izumo1. Expressed in: drosophila. Expression_system_taxid: 7215

Resolution:

2.10Å R-factor: 0.196 R-free: 0.231

Authors:

U.Ohto,H.Ishida,T.Shimizu

Key ref:

U.Ohto et al. (2016). Structure of IZUMO1-JUNO reveals sperm-oocyte recognition during mammalian fertilization. Nature, 534, 566-569. PubMed id: 27309808 DOI: 10.1038/nature18596

Date:

26-Apr-16 Release date: 22-Jun-16

Protein chains

Q8IYV9  (IZUM1_HUMAN) -  Izumo sperm-egg fusion protein 1 from Homo sapiens

Seq: 350 a.a.

Struc: 241 a.a.*

Protein chain

Q8IYV9  (IZUM1_HUMAN) -  Izumo sperm-egg fusion protein 1 from Homo sapiens

Seq: 350 a.a.

Struc: 212 a.a.*

* PDB and UniProt seqs differ at 11 residue positions (black crosses)

DOI no: 10.1038/nature18596

Nature 534:566-569 (2016)

PubMed id: 27309808

Structure of IZUMO1-JUNO reveals sperm-oocyte recognition during mammalian fertilization.

U.Ohto, H.Ishida, E.Krayukhina, S.Uchiyama, N.Inoue, T.Shimizu.

ABSTRACT

Fertilization is a fundamental process in sexual reproduction, creating a new individual through the combination of male and female gametes. The IZUMO1 sperm membrane protein and its counterpart oocyte receptor JUNO have been identified as essential factors for sperm-oocyte interaction and fusion. However, the mechanism underlying their specific recognition remains poorly defined. Here, we show the crystal structures of human IZUMO1, JUNO and the IZUMO1-JUNO complex, establishing the structural basis for the IZUMO1-JUNO-mediated sperm-oocyte interaction. IZUMO1 exhibits an elongated rod-shaped structure comprised of a helical bundle IZUMO domain and an immunoglobulin-like domain that are each firmly anchored to an intervening β-hairpin region through conserved disulfide bonds. The central β-hairpin region of IZUMO1 provides the main platform for JUNO binding, while the surface located behind the putative JUNO ligand binding pocket is involved in IZUMO1 binding. Structure-based mutagenesis analysis confirms the biological importance of the IZUMO1-JUNO interaction. This structure provides a major step towards elucidating an essential phase of fertilization and it will contribute to the development of new therapeutic interventions for fertility, such as contraceptive agents.