Proline-rich regions and motifs in trafficking: from ESCRT interaction to viral exploitation.

Proline-rich regions and motifs in trafficking: from ESCRT interaction to viral exploitation.
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DOI:
10.1111/j.1600-0854.2011.01208.x
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发表时间:
2011-10
期刊:
Traffic (Copenhagen, Denmark)
影响因子:
--
通讯作者:
Hurley JH
Hurley JH
中科院分区:
其他
文献类型:
--
作者:
Ren X;Hurley JH

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大多数膜包膜病毒通过劫持宿主ESCRT机制从被感染细胞中萌发。escrt被含有短的富含脯氨酸基序(PRMs)的病毒蛋白招募到芽点,这些PRMs被称为晚期结构域。晚期结构域可能是通过吸收参与escrt内体分选和细胞分裂正常功能的宿主PRMs而进化的。与其相互作用伙伴结合的PRMs的溶液和晶体结构解释了在这些序列中占主导地位的Pro和其他残基的保守作用。PRMs通常聚集在一个更大的富含脯氨酸的区域(PRRs)中,多达150个残基。escrt相关蛋白ALIX的PRR自动调节其构象和活性。不同的病毒出芽和宿主途径对脯氨酸相互作用损伤的稳健性差异很大。考虑到我们对宿主和病毒过程的相对弱点和健壮性日益细致的理解,ESCRT途径中富含脯氨酸基序识别的已知生物学原理原则上似乎与抗病毒开发相容。
Most membrane enveloped viruses bud from infected cells by hijacking the host ESCRT machinery. The ESCRTs are recruited to bud sites by viral proteins that contain short proline-rich motifs (PRMs) known as late domains. The late domains probably evolved by co-opting host PRMs involved in the normal functions of ESCRTs in endosomal sorting and cytokinesis. The solution and crystal structures of PRMs bound to their interaction partners explain the conserved roles of Pro and other residues that predominate in these sequences. PRMs are often grouped together in much larger proline-rich regions (PRRs) of as many as 150 residues. The PRR of the ESCRT-associated protein ALIX autoregulates its conformation and activity. The robustness of different viral budding and host pathways to impairments in proline-based interactions varies considerably. The known biology of proline rich motif recognition in the ESCRT pathway seems, in principle, compatible with antiviral development, given our increasingly nuanced understanding of the relative weakness and robustness of the host and viral processes.
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