For most retroviruses, including HIV, association with the plasma membrane (PM) promotes the assembly of immature particles, which occurs simultaneously with budding and maturation. In these viruses, maturation is initiated by oligomerization of polyprotein precursors. In contrast, several retroviruses, such as Mason-Pfizer monkey virus (M-PMV), assemble in the cytoplasm into immature particles that are transported across the PM. Therefore, protease activation and specific cleavage must not occur until the preassembled particle interacts with the PM. This interaction is triggered by a bipartite signal consisting of a cluster of basic residues in the matrix (MA) domain of Gag polyprotein and a myristoyl moiety N-terminally attached to MA. Here, we provide evidence that myristoyl exposure from the MA core and its insertion into the PM occurs in M-PMV. By a combination of experimental methods, we show that this results in a structural change at the C-terminus of MA allowing efficient cleavage of MA from the downstream region of Gag. This suggests that, in addition to the known effect of the myristoyl switch of HIV-1 MA on the multimerization state of Gag and particle assembly, the myristoyl switch may have a regulatory role in initiating sequential cleavage of M-PMV Gag in immature particles.

中文翻译：

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质膜上的肉豆蔻酰开关触发梅森-辉瑞猴病毒基质蛋白的裂解和寡聚化

对于大多数逆转录病毒，包括 HIV，与质膜 (PM) 的结合促进了未成熟颗粒的组装，这与出芽和成熟同时发生。在这些病毒中，成熟是通过多蛋白前体的寡聚化启动的。相比之下，一些逆转录病毒，例如梅森-辉瑞猴病毒（M-PMV），在细胞质中组装成不成熟的颗粒，然后通过 PM 运输。因此，在预组装颗粒与 PM 相互作用之前，蛋白酶激活和特异性裂解一定不会发生。这种相互作用是由二分信号触发的，该二分信号由 Gag 多蛋白基质 (MA) 结构域中的一组碱性残基和 N 端连接到 MA 的肉豆蔻酰基部分组成。在这里，我们提供的证据表明，M-PMV 中发生了从 MA 核心暴露肉豆蔻酰并将其插入 PM 的情况。通过结合实验方法，我们表明这会导致 MA C 末端的结构变化，从而使 MA 从 Gag 下游区域有效裂解。这表明，除了 HIV-1 MA 的肉豆蔻酰开关对 Gag 多聚化状态和颗粒组装的已知影响之外，肉豆蔻酰开关可能在启动未成熟颗粒中 M-PMV Gag 的顺序裂解中具有调节作用。