PDBsum entry 5f4t

Cell adhesion

PDB id: 5f4t

Contents

Protein chain

235 a.a.

Ligands

NAG

Waters ×4

PDB id:

5f4t

Name:

Cell adhesion

Title:

Crystal structure of the human sperm izumo1 residues 22-254

Structure:

Izumo sperm-egg fusion protein 1. Chain: a. Fragment: unp residues 22-254. Synonym: oocyte binding/fusion factor,obf,sperm-specific protein izumo. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: izumo1. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227

Resolution:

3.08Å R-factor: 0.221 R-free: 0.248

Authors:

H.Aydin,A.Sultana,J.E.Lee

Key ref:

H.Aydin et al. (2016). Molecular architecture of the human sperm IZUMO1 and egg JUNO fertilization complex. Nature, 534, 562-565. PubMed id: 27309818 DOI: 10.1038/nature18595

Date:

03-Dec-15 Release date: 15-Jun-16

Protein chain

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

Seq: 350 a.a.

Struc: 235 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1038/nature18595

Nature 534:562-565 (2016)

PubMed id: 27309818

Molecular architecture of the human sperm IZUMO1 and egg JUNO fertilization complex.

H.Aydin, A.Sultana, S.Li, A.Thavalingam, J.E.Lee.

ABSTRACT

Fertilization is an essential biological process in sexual reproduction and comprises a series of molecular interactions between the sperm and egg. The fusion of the haploid spermatozoon and oocyte is the culminating event in mammalian fertilization, enabling the creation of a new, genetically distinct diploid organism. The merger of two gametes is achieved through a two-step mechanism in which the sperm protein IZUMO1 on the equatorial segment of the acrosome-reacted sperm recognizes its receptor, JUNO, on the egg surface. This recognition is followed by the fusion of the two plasma membranes. IZUMO1 and JUNO proteins are indispensable for fertilization, as constitutive knockdown of either protein results in mice that are healthy but infertile. Despite their central importance in reproductive medicine, the molecular architectures of these proteins and the details of their functional roles in fertilization are not known. Here we present the crystal structures of human IZUMO1 and JUNO in unbound and bound conformations. The human IZUMO1 structure exhibits a distinct boomerang shape and provides structural insights into the IZUMO family of proteins. Human IZUMO1 forms a high-affinity complex with JUNO and undergoes a major conformational change within its N-terminal domain upon binding to the egg-surface receptor. Our results provide insights into the molecular basis of sperm-egg recognition, cross-species fertilization, and the barrier to polyspermy, thereby promising benefits for the rational development of non-hormonal contraceptives and fertility treatments for humans and other mammals.