Wolfsberg T G, Bazan J F, Blobel C P, Myles D G, Primakoff P, White J M
Department of Pharmacology, University of California, San Francisco 94143.
Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10783-7. doi: 10.1073/pnas.90.22.10783.
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.
PH - 30是一种参与精卵融合的精子表面蛋白，由α和β两个亚基组成，这两个亚基在精子发育过程中以前体形式合成并经过加工，从而产生成熟形式。成熟的PH - 30α/β复合物在膜拓扑结构以及预测的结合和融合功能方面类似于某些病毒融合蛋白。此外，成熟亚基彼此之间以及与一类含解整合素结构域的蛇毒蛋白在序列上相似。我们在此报告PH - 30α和β前体区域的序列。它们的结构域组织彼此相似，并且与蛇毒金属蛋白酶和解整合素的前体相似。α前体区域从氨基端到羧基端包含前肽、金属蛋白酶和解整合素结构域。β前体区域包含前肽和金属蛋白酶结构域。在α前体区域存在诊断催化活性金属蛋白酶的残基，而在β前体区域不存在。我们提出PH - 30α和蛇毒金属蛋白酶的活性位点在结构上与虾红素蛋白酶相似。PH - 30通过其金属蛋白酶和/或解整合素结构域发挥作用，可能参与精子发育以及精卵结合和融合。系统发育分析表明PH - 30起源于一种多结构域的祖先蛋白。
