STRUCTURAL REFINEMENT AND ANALYSIS OF MENGO-VIRUS
STRUCTURAL REFINEMENT AND ANALYSIS OF MENGO-VIRUS
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DOI：
10.1016/0022-2836(90)90077-y
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发表时间：
1990-02-20
影响因子：
5.6
通讯作者：
ROSSMANN, MG
中科院分区：
文献类型：
--
作者：
KRISHNASWAMY, S;ROSSMANN, MG
Mengo脑脊髓炎病毒的结构在3.ANG处被精制。最终R因子为0.221，与理想键长的均方根偏差为0.019埃。对于10. 3.安F ≥的数据3.sigma.（F）. Hendrickson-Konnert精修受到来自分子置换平均程序的相的限制，并受到病毒的二十面体对称性的约束。该病毒由60个启动子组成，每个启动子具有三个主要亚基，VP 1、VP 2和VP 3，沿着一个较小的内部蛋白，VP 4。三个主要亚基形成类似的八链β-桶形结构在VP 1的第45位（Arg至Ala）和VP 3的第58位（Met至瓦尔）发现原始序列的改变。VP 1环I和II中的残基（82至102），VP 1中的“FMDV环”（205至213），假定受体附着位点中的VP 3柔性环（175至185）以及在弱密度区域中构建或修饰了VP 1中的末端区域260至268、VP 2中的末端区域253至256和VP 4中的末端区域13至15。在细化结束时温度因子的变化在宽范围内（从2到80埃2），无序的外部和内部区域显示出高迁移率。已鉴定出4个顺式脯氨酸残基，VP 1中为105个，VP 2中为85个和152个，VP 3中为59个。VP 3中的二硫桥Cys 86至Cys 88已被表征。一个磷酸根离子和233个水位置被包括在改进中。这表明，这种磷酸盐与受体附着位点。有两个主要的氢键网络涉及溶剂原子;一个只涉及促进剂的亚基，另一个连接五聚体中的促进剂。二十面体对称轴周围的原子类型分布表明，5重通道比沿着3重轴更疏水，2重轴周围有更多的带电残基。不同亚基之间接触的分析支持原聚体单位的分配。形成五聚体单元的五个原聚体通过涉及较小的VP 4蛋白和VP 1和VP 3的氨基末端的相互作用而保持在一起。五聚体通过VP 2亚基的氨基末端区域、VP 3亚基的β F链、VP 4亚基的C末端和VP 2亚基跨二十面体2-折叠轴的静电螺旋（α A）相互作用而结合。Mengo病毒、人鼻病毒14和南方菜豆花叶病毒的相应亚基的重叠提供了改进的序列比对。Mengo病毒与鼻病毒的VP 3亚基结构相似性最大，VP 1亚基结构相似性最小。不同子单元中的各种专门插入可以与特定的功能需求相关联。
The structure of Mengo encephalomyelitis virus was refined at 3 .ANG. resolution with a final R-factor of 0.221 and a root-mean-square deviation from idealized bond lengths of 0.019 .ANG. for 10 .ANG. to 3 .ANG. data with F .gtoreq. 3.sigma.(F). The Hendrickson-Konnert refinement was restrained by the phases derived from the molecular replacement averaging procedure and constrained by the icosahedral symmetry of the virus. The virus consists of 60 promoters each having three major subunits, VP1, VP2, and VP3, along with one smaller internal protein, VP4. The three major subunits form similar eight-stranded .beta.-barrel structures. Alterations in the original sequence were found at position 45 in VP1 (Arg to Ala) and at position 58 in VP3 (Met to Val). The residues in loops I and II of VP1 (82 to 102), the "FMDV loop" in VP1 (205 to 213), the flexible loop of VP3 in the putative receptor attachment site (175 to 185) as well as the terminal regions 260 to 268 in VP1, 253 to 256 in VP2 and 13 to 15 in VP4 were built or modified in regions of weak density. The variation in temperature factors at the end of the refinement is over a wide range (from 2 to 80 .ANG.2), with the disordered outer and inner regions showing high mobility. Four cis proline residues, 105 in VP1, 85 and 152 in VP2 and 59 in VP3, have been identified. The disulfide bridge Cys86 to Cys88 in VP3 has been characterized. One phosphate ion and 233 water positions were included in the refinement. It is suggested that this phosphate is associated with the receptor attachment site. There are two major hydrogen-bonding networks involving solvent atoms; one involving only the subunits of a promoter, and the other connecting the promoters in a pentamer. The distribution of atom types around the icosahedral symmetry axes shows that the 5-fold channel is more hydrophobic than that along the 3-fold axis and that there are more charged residues around the 2-fold axis. The analysis of contacts between the different subunits supports the assignment of the protomeric unit. The five protomers that form the pentameric unit are held together by interactions involving the smaller VP4 protein and the amino termini of VP1 and VP3. The pentamers are associated by means of the amino-terminal region of the VP2 subunits, the .beta.F strand of the VP3 subunits, the C terminus of the VP4 subunits and the electrostatic helical (.alpha.A) interactions of VP2 subunits across the icosahedral 2-fold axes. The superposition of the corresponding subunits of Mengo virus, human rhinovirus 14 and southern bean mosaic virus has provided an improved sequence alignment. The largest structural similarity is between the VP3 subunits of Mengo virus and rhinovirus, while the least similarity is bewteen the VP1 subunits. The various specialized insertions in the different subunits can be associated with specific functional requirements.