Human Papillomavirus L2 Capsid Protein Stabilizes γ-Secretase during Viral Infection.
Human Papillomavirus L2 Capsid Protein Stabilizes γ-Secretase during Viral Infection.
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DOI：
10.3390/v14040804
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发表时间：
2022-04-13
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
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人乳头瘤病毒（HPV）在病毒进入细胞期间的细胞内运输需要γ-分泌酶，γ-分泌酶是一种由四种细胞跨膜（TM）蛋白的复合物组成的细胞蛋白酶。γ-分泌酶通常切割底物蛋白，但它在HPV进入过程中发挥非典型作用。γ-分泌酶与HPV次要衣壳蛋白L2结合，并促进其插入内体膜。插入后，L2突出到细胞质中，这使得HPV能够结合适当的病毒运输到逆行运输途径所需的其他细胞因子。在这里，我们进一步表征γ-分泌酶和HPV L2之间的相互作用。我们发现γ-分泌酶是L2细胞质突起所必需的，并且L2与γ-分泌酶的PS1催化亚基紧密结合并稳定γ-分泌酶复合物。突变研究表明，HPV 16 L2中推定的TM结构域不能被外源TM结构域取代，HPV TM突变体的感染性与γ-分泌酶结合和稳定性密切相关，并且L2 TM结构域是L2蛋白突出到细胞质中所必需的。这些结果为γ-分泌酶和L2之间的相互作用提供了新的见解，并强调了天然HPV L2 TM结构域在进入过程中对适当病毒运输的重要性。
Intracellular trafficking of human papillomavirus (HPV) during virus entry requires γ-secretase, a cellular protease consisting of a complex of four cellular transmembrane (TM) proteins. γ-secretase typically cleaves substrate proteins but it plays a non-canonical role during HPV entry. γ-secretase binds to the HPV minor capsid protein L2 and facilitates its insertion into the endosomal membrane. After insertion, L2 protrudes into the cytoplasm, which allows HPV to bind other cellular factors required for proper virus trafficking into the retrograde transport pathway. Here, we further characterize the interaction between γ-secretase and HPV L2. We show that γ-secretase is required for cytoplasmic protrusion of L2 and that L2 associates strongly with the PS1 catalytic subunit of γ-secretase and stabilizes the γ-secretase complex. Mutational studies revealed that a putative TM domain in HPV16 L2 cannot be replaced by a foreign TM domain, that infectivity of HPV TM mutants is tightly correlated with γ-secretase binding and stabilization, and that the L2 TM domain is required for protrusion of the L2 protein into the cytoplasm. These results provide new insight into the interaction between γ-secretase and L2 and highlight the importance of the native HPV L2 TM domain for proper virus trafficking during entry.
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影响因子：
6.7
作者：
Harwood MC;Dupzyk AJ;Inoue T;DiMaio D;Tsai B
通讯作者：
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DOI：
10.1007/978-3-030-57362-1_8
发表时间：
2021
期刊：
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
2.9
作者：
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通讯作者：
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