Aguilar Hector C, Anderson W French, Cannon Paula M
Gene Therapy Laboratories, Keck School of Medicine, University of Southern California, Los Angeles 90033, USA.
J Virol. 2003 Jan;77(2):1281-91. doi: 10.1128/jvi.77.2.1281-1291.2003.
The envelope (Env) protein of Moloney murine leukemia virus (MoMuLV) is a homotrimeric complex whose monomers consist of linked surface (SU) and transmembrane (TM) proteins cleaved from a precursor protein by a cellular protease. In addition, a significant fraction of virion-associated TM is further processed by the viral protease to remove the C-terminal 16 amino acids of the cytoplasmic domain, the R peptide. This cleavage greatly enhances the fusogenicity of the protein and is necessary for the formation of a fully functional Env protein complex. We have previously proposed that R peptide cleavage enhances fusogenicity by altering the conformation of the ectodomain of the protein (Y. Zhao et al., J. Virol. 72:5392-5398, 1998). Using a series of truncation and point mutants of MoMuLV Env, we now provide direct biochemical and immunological evidence that the cytoplasmic tail and the membrane-spanning region of Env can influence the overall structure of the ectodomain of the protein and alter the strength of the SU-TM interaction. The R-peptide-truncated form of the protein, in particular, exhibits a markedly different conformation than the full-length protein.
莫洛尼鼠白血病病毒（MoMuLV）的包膜（Env）蛋白是一种同源三聚体复合物，其单体由通过细胞蛋白酶从前体蛋白切割而来的相连的表面（SU）蛋白和跨膜（TM）蛋白组成。此外，很大一部分与病毒粒子相关的TM会被病毒蛋白酶进一步加工，以去除细胞质结构域的C末端16个氨基酸，即R肽。这种切割极大地增强了该蛋白的融合活性，并且对于形成功能完全的Env蛋白复合物是必需的。我们之前曾提出，R肽切割通过改变该蛋白胞外域的构象来增强融合活性（Y. Zhao等人，《病毒学杂志》72:5392 - 5398，1998年）。现在，我们利用一系列MoMuLV Env的截短突变体和点突变体，提供了直接的生化和免疫学证据，证明Env的细胞质尾巴和跨膜区域能够影响该蛋白胞外域的整体结构，并改变SU - TM相互作用的强度。特别是，该蛋白的R肽截短形式表现出与全长蛋白明显不同的构象。
