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The precursor region of a protein active in sperm-egg fusion contains a metalloprotease and a disintegrin domain:
T G Wolfsberg1, J F Bazan, C P Blobel
1Department of Pharmacology, University of California, San Francisco 94143.
Abstract:
PH-30, a sperm surface protein involved in sperm-egg fusion, is composed of two subunits, alpha and beta, which are synthesized as precursors and processed, during sperm development, to yield the mature forms. The mature PH-30 alpha/beta complex resembles certain viral fusion proteins in membrane topology and predicted binding and fusion functions. Furthermore, the mature subunits are similar in sequence to each other and to a family of disintegrin domain-containing snake venom proteins. We report here the sequences of the PH-30 alpha and beta precursor regions. Their domain organizations are similar to each other and to precursors of snake venom metalloproteases and disintegrins. The alpha precursor region contains, from amino to carboxyl terminus, pro, metalloprotease, and disintegrin domains. The beta precursor region contains pro and metalloprotease domains. Residues diagnostic of a catalytically active metalloprotease are present in the alpha, but not the beta, precursor region. We propose that the active sites of the PH-30 alpha and snake venom metalloproteases are structurally similar to that of astacin. PH-30, acting through its metalloprotease and/or disintegrin domains, could be involved in sperm development as well as sperm-egg binding and fusion. Phylogenetic analysis indicates that PH-30 stems from a multidomain ancestral protein.
Insights
PH-30, a sperm protein essential for fertilization, shares structural similarities with viral fusion proteins and snake venom proteins. Its precursor regions contain domains suggesting roles in sperm development and egg fusion.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Biochemistry
Background:
- PH-30 is a sperm surface protein crucial for sperm-egg fusion.
- It consists of alpha and beta subunits, synthesized as precursors and processed into mature forms.
- The mature PH-30 complex shares similarities with viral fusion proteins and snake venom proteins.
Purpose of the Study:
- To determine the sequences of the PH-30 alpha and beta precursor regions.
- To analyze the domain organization and evolutionary origins of PH-30.
- To investigate the potential roles of PH-30 domains in sperm function.
Main Methods:
- Sequence analysis of PH-30 precursor regions.
- Domain organization comparison with snake venom proteins.
- Phylogenetic analysis.
Main Results:
- PH-30 alpha and beta precursor regions exhibit similar domain organizations.
- The alpha precursor contains pro, metalloprotease, and disintegrin domains; the beta precursor contains pro and metalloprotease domains.
- PH-30 alpha contains residues indicative of a catalytically active metalloprotease, similar to astacin.
Conclusions:
- PH-30 likely evolved from a multidomain ancestral protein.
- Its metalloprotease and disintegrin domains may play roles in sperm development and fertilization.
- PH-30 represents a link between viral fusion proteins and snake venom proteins.