Volk David E, Beasley David W C, Kallick Deborah A, Holbrook Michael R, Barrett Alan D T, Gorenstein David G
Sealy Center for Structural Biology, University of Texas Medical Branch, Galveston, Texas 77555-1147, USA.
J Biol Chem. 2004 Sep 10;279(37):38755-61. doi: 10.1074/jbc.M402385200. Epub 2004 Jun 9.
The solution structure of domain III from the New York West Nile virus strain 385-99 (WN-rED3) has been determined by NMR methods. The West Nile domain III structure is a beta-barrel structure formed from seven anti-parallel beta-strands in two beta-sheets. One anti-parallel beta-sheet consists of beta-strands beta1 (Phe(299)-Asp(307)), beta2 (Val(313)-Tyr(319)), beta4 (Arg(354)-Leu(355)), and beta5 (Lys(370)-Glu(376)) arranged so that beta2 is flanked on either side by beta1 and beta5. The short beta4 flanks the end of the remaining side of beta5. The remaining anti-parallel beta-sheet is formed from strands beta3 (Ile(340)-Val(343)), beta6 (Gly(380)-Arg(388)), and beta7 (Gln(391)-Lys(399)) arranged with beta6 at the center. Residues implicated in antigenic differences between different West Nile virus strains (and other flaviviruses) and neutralization are located on the outer surface of the protein. Characterization of the binding of monoclonal antibodies to WN-rED3 mutants, which were identified through neutralization escape experiments, indicate that antibody neutralization directly correlates with binding affinities. These studies provide an insight into theoretical virus-receptor interaction points, structure of immunogenic determinants, and potential targets for antiviral agents against West Nile virus and highlight differences between West Nile virus and other flavivirus structures that may represent critical determinants of virulence.
通过核磁共振方法确定了纽约西尼罗河病毒株385 - 99（WN - rED3）结构域III的溶液结构。西尼罗河病毒结构域III的结构是一个β桶结构，由两个β折叠中的七条反平行β链组成。一个反平行β折叠由β链β1（苯丙氨酸（299） - 天冬氨酸（307））、β2（缬氨酸（313） - 酪氨酸（319））、β4（精氨酸（354） - 亮氨酸（355））和β5（赖氨酸（370） - 谷氨酸（376））组成，其排列方式使得β2的两侧分别为β1和β5。短的β4位于β5另一侧末端的旁边。其余的反平行β折叠由β链β3（异亮氨酸（340） - 缬氨酸（343））、β6（甘氨酸（380） - 精氨酸（388））和β7（谷氨酰胺（391） - 赖氨酸（399））组成，β6位于中心。与不同西尼罗河病毒株（以及其他黄病毒）之间的抗原差异和中和作用相关的残基位于蛋白质的外表面。对通过中和逃逸实验鉴定的WN - rED3突变体与单克隆抗体结合的表征表明，抗体中和作用与结合亲和力直接相关。这些研究为理论上的病毒 - 受体相互作用点、免疫原性决定簇的结构以及抗西尼罗河病毒抗病毒药物的潜在靶点提供了见解，并突出了西尼罗河病毒与其他黄病毒结构之间的差异，这些差异可能是毒力的关键决定因素。
