Researchers identify new architecture and mechanism in the human sperm.

In male fertility normal sperm cells have an oval-shaped head with a cap-like covering called the acrosome. The acrosome contains enzymes that break down the outer membrane of an egg cell, allowing the sperm to fertilize the egg. One of the causes of male infertility is abnormally shaped sperm. About 60% of the sperm should be normal in size and shape for adequate fertility. The perfect sperm structure is an oval head and long tail, much research covers this aspect of male infertility as-well-as a low sperm count.

Now, a 14-year study from researchers at the University of Virginia shows that a protein within the head of the sperm forms spiky filaments, suggesting that these tiny filaments may lash together the sperm and its target, causing the sperm to harpoon the egg to enable fertilisation.  The team state that their study represents a significant step forward in the fine dissection of the protein architecture of the sperm’s acrosomal matrix, an organelle in the sperm head, and suggests a new hypothesis concerning what happens during fertilization. The study is published in the journal Andrology.

In earlier studies the lab discovered the protein, which they named sperm lysozyme-like protein 1 (SLLP1), that has now been shown to form the filaments. The protein is a member of a family of proteins now known to reside inside the acrosome.  However, the team had no way to determine the shape and structure of the protein.

To enable this the current study had to capture the protein within a static crystal, cool the crystal to cryogenic temperatures to prevent decay and then blast it with X-rays. By examining how those X-rays were refracted, they could calculate the shape of the protein, somewhat like mapping out a shipwreck with sonar.  After many attempts the researchers were able to produce one of the first descriptions of a sperm protein.

The group note that this is an important protein, because it’s the first crystal structure from a protein within the sperm acrosome.  They go on to add that it is also the first structure of a mammalian sperm protein with a specific oocyte-side binding partner characterized. To the researchers knowledge, only nine proteins specifically obtained from mammalian sperm have known structures.

The results show that one of the major proteins that is abundant in the acrosome, in the arterior region of the sperm head, is crystallizing into filaments.  The team now postulate they’re involved in penetrating the egg, which leads to a whole new set of questions and new hypotheses about the very fine structure of molecular events during fertilization.

The lab surmise that new understanding of the structure will now act as a map for the global medical community exploring how fertilization occurs. They go on to conclude that at the very fundamental level, understanding that fine molecular architecture leads them to be able to posit new functions for this family of proteins discovered in the acrosome.

Source:  University of Virginia School of Medicine


The SLLP1 filament viewed along the side, with each neighboring monomer colored alternatively.  Credit:  Heping Zheng, Ph.D., University of Virginia School of Medicine.
The SLLP1 filament viewed along the side, with each neighboring monomer colored alternatively. Credit: Heping Zheng, Ph.D., University of Virginia School of Medicine.



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