THE INFLUENZA HEMAGGLUTININ PRECURSOR AS AN ACID-SENSITIVE PROBE OF THE BIOSYNTHETIC-PATHWAY
THE INFLUENZA HEMAGGLUTININ PRECURSOR AS AN ACID-SENSITIVE PROBE OF THE BIOSYNTHETIC-PATHWAY
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DOI：
10.1002/j.1460-2075.1987.tb02555.x
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发表时间：
1987-09-01
期刊：
影响因子：
11.4
通讯作者：
HELENIUS, A
中科院分区：
文献类型：
--
作者：
BOULAY, F;DOMS, RW;HELENIUS, A
流感病毒的血凝素（HA）是一种酸活化的膜融合蛋白，在内质网中合成，并作为未切割的、不具有融合能力的前体HA 0通过高尔基复合体转运到感染细胞的细胞表面。已知成熟的蛋白水解活化的HA经历快速的、不可逆的、酸诱导的构象变化，其介导膜融合和病毒穿透。抗原修饰和胰蛋白酶亲和性的收购的基础上，我们在这里证明，HA0，而不能引起融合，是酸敏感的。它在弱酸性pH（pH < 6.0）下经历与HA非常相似的不可逆构象变化。然而，HA0的胞外域没有获得疏水性质，并且变化以不太协调的方式发生（pH依赖性更广泛，转化速率更慢）。这些差异可能是酸处理的HA0不能触发膜融合的原因。它表明，此外，HA0获得其酸敏感特性后，立即在内质网中的三聚体。由于HA0在其细胞内转运过程中的任何时候都没有转化为酸形式，我们得出结论，已知比胞质溶胶酸性更强并参与组成性膜转运的反式高尔基体区室不太可能具有pH < 6.0。
The hemagglutinin of influenza virus (HA), an acid-activated membrane fusion protein, is synthesized in the endoplasmic reticulum and transported through the Golgi complex to the cell surface of infected cells as an uncleaved, fusion-incompetent precursor, HA0. The mature, proteolytically activated HA is known to undergo a rapid, irreversible, acid-induced conformational change which mediates membrane fusion and virus penetration. On the basis of antigenic modifications and the acquisition of trypsin susceptiblity, we demonstrate here that HA0, while unable to cause fusion, is acid sensitive. It undergoes irreversible conformational changes quite similar to those of HA at mildly acidic pH (pH < 6.0). The ectodomain of HA0 does not, however, acquire hydrophobic properties and the changes occur in a less concerted manner (the pH dependence is much broader and the rate of conversion slower). These differences are likely to account for the inability of acid-treated HA0 to trigger membrane fusion. It was shown, moreover, that HA0 acquired its acid-sensitive properties immediately following trimerization in the endoplasmic reticulum. Since HA0 did not convert to the acid form at any point during its intracellular transport, we concluded that the trans-Golgi compartment, known to be more acidic than the cytosol and involved in constitutive membrane transport, is not likely to have a pH < 6.0.