A long-standing mystery in developmental biology and reproductive medicine involves the fusion of sperm and egg membranes. It was only in 2005 that Izumo1, the sperm protein essential for this fusion, was identified. And it was only two years ago that the receptor of Izumo1, named Juno, was discovered on the surface of the mature human egg.
In this study, researchers from the University of Toronto determined the crystal structures of human Izumo1 and Juno, alone and in complex. These are the first atomic-resolution structures of any protein complex between sperm and egg at the point of conception for any organism. The researchers used primarily three techniques: x-ray crystallography at the Canadian Light Source, small-angle x-ray scattering (SAXS) at ALS Beamline 12.3.1, and deuterium exchange mass spectrometry (DXMS) at UC San Diego.
The SAXS, crystallographic, and comparative DXMS studies revealed that the boomerang-shaped Izumo1 has an architecture that is completely different from other viral and cellular fusion proteins. It locks into an upright conformation upon binding to Juno, possibly one of the structural changes necessary for fusion. The structures provide much-needed basic information on the mechanisms of sperm–egg recognition and fusion machinery and provide crucial leads for the development of non-hormonal contraceptives and fertility treatments for humans and other mammals.
Overall, the results build a foundation for further characterization of the interactions of sperm and egg and provide an updated model to understand the fundamental principles of the mammalian fertilization and fusion process.
SAXS performed at ALS Beamline 12.3.1.
H. Aydin, A. Sultana, S. Li, A. Thavalingam, and J.E. Lee, “Molecular architecture of the human sperm IZUMO1 and egg JUNO fertilization complex,” Nature 534, 562 (2016).