STUDIES ON THE FUSION PEPTIDE OF A PARAMYXOVIRUS FUSION GLYCOPROTEIN - ROLES OF CONSERVED RESIDUES IN CELL-FUSION
STUDIES ON THE FUSION PEPTIDE OF A PARAMYXOVIRUS FUSION GLYCOPROTEIN - ROLES OF CONSERVED RESIDUES IN CELL-FUSION
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DOI：
10.1128/jvi.66.4.2443-2455.1992
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发表时间：
1992-04-01
影响因子：
5.4
通讯作者：
LAMB, RA
中科院分区：
文献类型：
--
作者：
HORVATH, CM;LAMB, RA
研究了副粘病毒融合（F）蛋白的保守疏水性N端融合肽中的残基在引起细胞-细胞融合中的作用。将突变引入编码猿猴病毒5（SV5）F蛋白的cDNA中，使用真核载体表达改变的F蛋白，并测定它们介导合胞体形成的能力。突变F蛋白含有单氨基酸和多氨基酸取代，并且它们表现出多种细胞内转运特性和融合表型。数据表明，猿猴病毒5F融合肽的保守氨基酸中的许多取代是可以耐受的，而不损失生物活性。未转运至细胞表面的突变体F蛋白不会引起细胞与细胞的融合，但所有转运至细胞表面的突变体均具有融合能力，表现出与野生型F蛋白相似或更好的融合特性。含有甘氨酸至丙氨酸取代的突变体 F 蛋白改变了细胞内转运特性，但它们表现出融合活性的大幅增加。讨论了这种取代的潜在结构含义以及这些甘氨酸残基在维持适当水平的融合活性方面可能的重要性。
The role of residues in the conserved hydrophobic N-terminal fusion peptide of the paramyxovirus fusion (F) protein in causing cell-cell fusion was examined. Mutations were introduced into the cDNA encoding the simian virus 5 (SV5) F protein, the altered F proteins were expressed by using an eukaryotic vector, and their ability to mediate syncytium formation was determined. The mutant F proteins contained both single- and multiple-amino-acid substitutions, and they exhibited a variety of intracellular transport properties and fusion phenotypes. The data indicate that many substitutions in the conserved amino acids of the simian virus 5 F fusion peptide can be tolerated without loss of biological activity. Mutant F proteins which were not transported to the cell surface did not cause cell-cell fusion, but all of the mutants which were transported to the cell surface were fusion competent, exhibiting fusion properties similar to or better than those of the wild-type F protein. Mutant F proteins containing glycine-to-alanine substitutions had altered intracellular transport characteristics, yet they exhibited a great increase in fusion activity. The potential structural implications of this substitution and the possible importance of these glycine residues in maintaining appropriate levels of fusion activity are discussed.