A supraphysiological nuclear export signal is required for parvovirus nuclear export
A supraphysiological nuclear export signal is required for parvovirus nuclear export
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DOI：
10.1091/mbc.e08-01-0009
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发表时间：
2008-06-01
影响因子：
3.3
通讯作者：
Fornerod, Maarten
中科院分区：
文献类型：
--
作者：
Engelsma, Dieuwke;Valle, Noelia;Fornerod, Maarten
CRM1从细胞核输出携带短的富含亮氨酸的肽信号的蛋白质，即核输出信号（内斯）。常规NES必须对CRM1具有低亲和力才能发挥最佳功能。我们以前产生的人工NES与CRM1的亲和力较高，称为超生理NES。在这里，我们确定了一个超生理内斯的内源性蛋白质，NS2蛋白的细小病毒细小病毒的小鼠（MVM）。NS2与CRM 1相互作用而不需要RanGTP，而RanGTP的加入使复合物高度稳定。使常规NES失活的单个疏水残基的突变降低了NS2内斯对CRM 1的亲和力，从超生理性降低到常规性。携带这种常规内斯的突变MVM在病毒核输出和生产力方面受到损害。在病毒感染的小鼠成纤维细胞中，我们观察到NS2、CRM 1和成熟病毒粒子的共定位，这依赖于超生理学的NS2内斯。我们得出结论，超生理NES存在于自然界中，超生理NS2内斯在细胞裂解前成熟MVM颗粒的主动核输出中具有关键作用。
CRM1 exports proteins that carry a short leucine-rich peptide signal, the nuclear export signal (NES), from the nucleus. Regular NESs must have low affinity for CRM1 to function optimally. We previously generated artificial NESs with higher affinities for CRM1, termed supraphysiological NESs. Here we identify a supraphysiological NES in an endogenous protein, the NS2 protein of parvovirus Minute Virus of Mice (MVM). NS2 interacts with CRM1 without the requirement of RanGTP, whereas addition of RanGTP renders the complex highly stable. Mutation of a single hydrophobic residue that inactivates regular NESs lowers the affinity of the NS2 NES for CRM1 from supraphysiological to regular. Mutant MVM harboring this regular NES is compromised in viral nuclear export and productivity. In virus-infected mouse fibroblasts we observe colocalization of NS2, CRM1 and mature virions, which is dependent on the supraphysiological NS2 NES. We conclude that supraphysiological NESs exist in nature and that the supraphysiological NS2 NES has a critical role in active nuclear export of mature MVM particles before cell lysis.