5F4V

Crystal structure of the human sperm Izumo1 residues 22-268

Summary for 5F4V

• Entry DOI: 10.2210/pdb5f4v/pdb
• Related: 5F4E 5F4Q 5F4T
• Descriptor: Izumo sperm-egg fusion protein 1, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: glycoprotein, membrane-bound, cysteine-rich, adhesion, fusion, cell adhesion
• Biological source: Homo sapiens (Human)
• Cellular location: Cell membrane ; Single-pass type I membrane protein : Q8IYV9
• Total number of polymer chains: 1
• Total formula weight: 29001.37

Authors

Aydin, H.,Sultana, A.,Lee, J.E. (deposition date: 2015-12-03, release date: 2016-06-15, Last modification date: 2024-10-23)

Primary citation

Aydin, H.,Sultana, A.,Li, S.,Thavalingam, A.,Lee, J.E.
Molecular architecture of the human sperm IZUMO1 and egg JUNO fertilization complex.
Nature, 534:562-565, 2016

PubMed 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.

PubMed: 27309818
DOI: 10.1038/nature18595

Experimental method

X-RAY DIFFRACTION (2.9 Å)