Amino acid substitutions in the F-Specific domain in the stalk of the Newcastle disease virus HN protein modulate fusion and interfere with its interaction with the F protein
Amino acid substitutions in the F-Specific domain in the stalk of the Newcastle disease virus HN protein modulate fusion and interfere with its interaction with the F protein
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DOI：
10.1128/jvi.78.23.13053-13061.2004
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发表时间：
2004-12-01
影响因子：
5.4
通讯作者：
Iorio, RM
中科院分区：
文献类型：
--
作者：
Melanson, VR;Iorio, RM
新城疫病毒的血凝素神经氨酸酶(HN)蛋白介导与唾液酸受体的结合以及同一部分的裂解。HN还与另一种病毒糖蛋白-融合(F)蛋白相互作用，促进膜融合。HN穗的外域由柄和顶端球状头部组成。茎中最保守的部分由两个七肽重复组成，中间有一个非螺旋区域(残基89到95)。该区域一个完全保守的氨基酸残基的几个氨基酸替换不仅破坏了融合和HN-F相互作用，而且还降低了球状结构域中神经氨酸酶的活性，表明这些替换可能改变了HN的结构。L94的替换也干扰了融合和HN-F相互作用，但对任何其他HN功能没有显著影响。在中间区域的其他位置的氨基酸替换也只调节融合。在所有情况下，融合减少与突变的HN蛋白在细胞表面与F相互作用的能力降低相关。这些发现表明，介入区对HN在促进融合中的作用至关重要，并可能直接参与HN与同源F蛋白的相互作用。
The hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus mediates attachment to sialic acid receptors, as well as cleavage of the same moiety. HN also interacts with the other viral glycoprotein, the fusion (F) protein, to promote membrane fusion. The ectodomain of the HN spike consists of a stalk and a terminal globular head. The most conserved part of the stalk consists of two heptad repeats separated by a nonhelical intervening region (residues 89 to 95). Several amino acid substitutions for a completely conserved proline residue in this region not only impair fusion and the HN-F interaction but also decrease neuraminidase activity in the globular domain, suggesting that the substitutions may alter HN structure. Substitutions for L94 also interfere with fusion and the HN-F interaction but have no significant effect on any other HN function. Amino acid substitutions at other positions in the intervening region also modulate only fusion. In all cases, diminished fusion correlates with a decreased ability of the mutated HN protein to interact with F at the cell surface. These findings indicate that the intervening region is critical to the role of HN in the promotion of fusion and may be directly involved in its interaction with the homologous F protein.