Murine norovirus protein NS1/2 aspartate to glutamate mutation, sufficient for persistence, reorients side chain of surface exposed tryptophan within a novel structured domain.
Murine norovirus protein NS1/2 aspartate to glutamate mutation, sufficient for persistence, reorients side chain of surface exposed tryptophan within a novel structured domain.
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DOI：
10.1002/prot.24484
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发表时间：
2014-07
影响因子：
2.9
通讯作者：
Krezel, Andrzej M.
中科院分区：
文献类型：
--
作者：
Borin, Brendan N.;Tang, Wei;Nice, Timothy J.;McCune, Broc T.;Virgin, Herbert W.;Krezel, Andrzej M.
紧凑的病毒基因组，例如在诺如病毒中发现的病毒基因组，通常只编码少数蛋白质，但影响其宿主的广泛过程，并确保病毒的有效繁殖。诺如病毒可引起人类严重的肠道疾病。人和小鼠诺如病毒都能持续复制并通过粪便排出，这是在宿主之间传播的一种非常有效的策略。对于小鼠诺如病毒（MNV）， NS1/2蛋白的第94位存在谷氨酸而不是天冬氨酸，先前已被证明是持续复制和脱落所必需的。本文从结构层面对NS1/2的关键序列进行分析。利用溶液核磁共振方法，我们确定了非持续性小鼠诺如病毒菌株CW3、持续性菌株CR6和持续性突变株CW3D94E的NS1/2结构域的折叠结构。我们在NS1/2的n端发现了一个非结构化的类似pest的结构域，后面跟着一个新的折叠结构域。这三种形式的结构域在溶液中都是稳定的单体。残基94是决定持久性的关键，它位于折叠结构域α-螺旋的反转位置。谷氨酸较长的侧链，而不是天冬氨酸，允许与附近色氨酸的吲哚基团相互作用，重塑结构域的表面。谷氨酰基和天冬氨酸残基之间的区别是由稳定的三级构象决定的。这些结构要求与NS1/2在体内的持久性功能相关，这是诺如病毒生物学和感染的关键因素。
Compact viral genomes such as those found in noroviruses, which cause significant enteric disease in humans, often encode only a few proteins, but affect a wide range of processes in their hosts and ensure efficient propagation of the virus. Both human and mouse noroviruses persistently replicate and are shed in stool, a highly effective strategy for spreading between hosts. For mouse norovirus (MNV), the presence of a glutamate rather than an aspartate at position 94 of the NS1/2 protein was previously shown to be essential for persistent replication and shedding. Here, we analyze these critical sequences of NS1/2 at the structural level. Using solution NMR methods we determined folded NS1/2 domain structures from a nonpersistent murine norovirus strain CW3, a persistent strain CR6, and a persistent mutant strain CW3D94E. We found an unstructured PEST-like domain followed by a novel folded domain in the N-terminus of NS1/2. All three forms of the domain are stable and monomeric in solution. Residue 94, critical for determining persistence, is located in a reverse turn following an α-helix in the folded domain. The longer sidechain of glutamate, but not aspartate, allows interaction with the indole group of the nearby tryptophan, reshaping the surface of the domain. The discrimination between glutamyl and aspartyl residue is imposed by the stable tertiary conformation. These structural requirements correlate with the in vivo function of NS1/2 in persistence, a key element of norovirus biology and infection.
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影响因子：
56.9
作者：
Karst, SM;Wobus, CE;Virgin, HW
通讯作者：
Virgin, HW
DOI：
10.1038/nsb740
发表时间：
2002-01-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Gross, E;Sevier, CS;Fass, D
通讯作者：
Fass, D
影响因子：
9.4
作者：
Sukhrie, Faizel H. A.;Siebenga, J. Joukje;Koopmans, Marion
通讯作者：
Koopmans, Marion
影响因子：
5.4
作者：
Lepere-Douard, Charlotte;Trotard, Maud;Gripon, Philippe
通讯作者：
Gripon, Philippe
影响因子：
56.9
作者：
ROGERS, S;WELLS, R;RECHSTEINER, M
通讯作者：
RECHSTEINER, M