Gan Siok Wan, Xin Lin, Torres Jaume
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.
Protein Sci. 2007 Feb;16(2):285-92. doi: 10.1110/ps.062494307. Epub 2006 Dec 22.
Fertilin is a transmembrane protein heterodimer formed by the two subunits fertilin alpha and fertilin beta that plays an important role in sperm-egg fusion. Fertilin alpha and beta are members of the ADAM family, and contain each one transmembrane alpha-helix, and are termed ADAM 1 and ADAM 2, respectively. ADAM 1 is the subunit that contains a putative fusion peptide, and we have explored the possibility that the transmembrane alpha-helical domain of ADAM 1 forms homotrimers, in common with other viral fusion proteins. Although this peptide was found to form various homooligomers in SDS, the infrared dichroic data obtained with the isotopically labeled peptide at specific positions is consistent with the presence of only one species in DMPC or POPC lipid bilayers. Comparison of the experimental orientational data with molecular dynamics simulations performed with sequence homologues of ADAM 1 show that the species present in lipid bilayers is only consistent with an evolutionarily conserved homotrimeric model for which we provide a backbone structure. These results support a model where ADAM 1 forms homotrimers as a step to create a fusion active intermediate.
受精素是一种跨膜蛋白异二聚体，由受精素α和受精素β两个亚基组成，在精卵融合中起重要作用。受精素α和β是ADAM家族的成员，各自含有一个跨膜α螺旋，分别被称为ADAM 1和ADAM 2。ADAM 1是包含一个假定融合肽的亚基，我们探讨了ADAM 1的跨膜α螺旋结构域与其他病毒融合蛋白一样形成同三聚体的可能性。尽管发现该肽在SDS中形成各种同寡聚体，但在特定位置用同位素标记的肽获得的红外二向色性数据与在DMPC或POPC脂质双层中仅存在一种物质一致。将实验取向数据与用ADAM 1的序列同源物进行的分子动力学模拟进行比较表明，脂质双层中存在的物质仅与我们提供主链结构的进化保守同三聚体模型一致。这些结果支持了一个模型，即ADAM 1形成同三聚体是创建融合活性中间体的一个步骤。
