Sergel T, McGinnes L, Morrison T
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655.
Virus Res. 1993 Dec;30(3):281-94. doi: 10.1016/0168-1702(93)90096-6.
The hemagglutinin-neuraminidase (HN) proteins of viruses in the Paramyxovirus genus have a short conserved sequence, G(A, S)EGR(I, L, V). The role of this sequence in the intracellular processing and function of the Newcastle disease virus HN protein was explored by site directed mutagenesis. Mutations in this region fall into two categories. One set of mutants (G398A, E400D, R402K, and a deletion removing amino acids 400-403) was defective in folding. These mutant proteins formed little or no mature, disulfide linked oligomer. They had few or no antigenic sites found on the mature protein and they were transported to the cell surface poorly or not at all. The second class of mutants (A399G, G401A, G401L) was minimally affected in folding and intracellular transport. When normalized to surface expression, this group of mutant proteins had wild type levels of attachment activity, neuraminidase activity, and fusion promotion activity. Thus mutations in this region directly affect intracellular processing but not the biological activities of the protein. This sequence may, therefore, be conserved in the HN proteins of Paramyxoviruses because it is critical to the folding of the molecule.
副粘病毒属病毒的血凝素神经氨酸酶（HN）蛋白有一段短保守序列，即G(A, S)EGR(I, L, V)。通过定点诱变研究了该序列在新城疫病毒HN蛋白细胞内加工及功能中的作用。该区域的突变分为两类。一组突变体（G398A、E400D、R402K以及缺失400 - 403位氨基酸）在折叠方面存在缺陷。这些突变蛋白几乎不形成或完全不形成成熟的、二硫键连接的寡聚体。它们在成熟蛋白上几乎没有或完全没有抗原位点，并且向细胞表面的转运很差或根本无法转运。第二类突变体（A399G、G401A、G401L）在折叠和细胞内转运方面受到的影响最小。当将表面表达标准化后，这组突变蛋白具有野生型水平的附着活性、神经氨酸酶活性和融合促进活性。因此，该区域的突变直接影响细胞内加工，但不影响蛋白的生物学活性。所以，这段序列可能在副粘病毒的HN蛋白中保守，因为它对分子的折叠至关重要。
