Structural predictions of AgfA, the insoluble fimbrial subunit of Salmonella thin aggregative fimbriae
Structural predictions of AgfA, the insoluble fimbrial subunit of Salmonella thin aggregative fimbriae
复制标题
DOI：
10.1006/jmbi.1999.2882
复制
发表时间：
1999-07-16
影响因子：
5.6
通讯作者：
Kay, WW
中科院分区：
文献类型：
--
作者：
Collinson, SK;Parker, JMR;Kay, WW
所有沙门氏菌常见的异常稳定和多功能的薄聚集菌毛主要是纤蛋白亚基AgfA的聚合物。肠炎沙门氏菌AgfA由两个结构域组成：蛋白酶敏感的22个氨基酸残基n端区域和蛋白酶抗性的109个氨基酸残基c端核心。AgfA核心区域不寻常的氨基酸序列包括2倍、5倍和10倍的内部序列同源模式，反映在5个保守的18个残基串联重复序列中。这些重复序列具有一致序列Sx(5)QxGx(2)NxAx(3)Q，并由四个或五个残基(x)xAx(2)连接在一起。AgfA中这种不寻常的串联重复序列的预测二级结构表明，β链主要是由4到6个残基连接的延伸构象。从SCOP中描述的折叠中选择具有β链和短环交替基序的已知结构的候选蛋白作为AgfA模型构建的坐标来源。从粘质沙雷氏菌金属蛋白酶、髓磷脂P2蛋白或卵黄膜外蛋白I中选择三个全β类基序用于初始AgfA同源构建程序，最终得到三个结构模型；圆柱体，棱镜，平行螺旋。贝塔桶模型是一个紧凑的，尽管不规则的结构，与贝塔股排列在两个反平行的贝塔片面。β棱镜模型不能反映AgfA初级序列的5或10倍对称性。然而，最受欢迎的平行β螺旋模型是由十个螺旋排列的β链组成的紧凑线圈，形成两个平行的β片面。这种排列预示着一个规则的、潜在稳定的、与观察到的串联重复序列一致的c端核心区域、蛋白酶抗性以及这种纤维蛋白低聚和聚集的强烈倾向。AgfA和大肠杆菌AgfA同源物CsgA中氨基酸残基的位置保守性为该模型提供了强有力的支持。AgfA的平行β螺旋模型为多功能纤维蛋白分子表面提供了一个有趣的解决方案，该分子表面具有溶剂暴露区，主要和次要亚基相互作用区域以及许多细菌纤维常见的纤维-纤维相互作用。(C) 1999学术出版社。
The unusually stable and multifunctional, thin aggregative fimbriae common to all Salmonella spp. are principally polymers of the fimbrin subunit, AgfA. AgfA of Salmonella enteritidis consists of two domains: a protease-sensitive, 22 amino acid residue N-terminal region and a protease-resistant, 109 residue C-terminal core. The unusual amino acid sequence of the AgfA core region comprises two-, five- and tenfold internal sequence homology patterns reflected in five conserved, 18-residue tandem repeats. These repeats have the consensus sequence, Sx(5)QxGx(2)NxAx(3)Q and are linked together by four or five residues, (x)xAx(2). The predicted secondary structure for this unusual arrangement of tandem repeats in AgfA indicates mainly extended conformation with the beta strands linked by four to six residues. Candidate proteins of known structure with motifs of alternating beta strands and short loops were selected from folds described in SCOP as a source of coordinates for AgfA model construction. Three all-beta class motifs selected from the Serratia marcescens metalloprotease, myelin P2 protein or vitelline membrane outer protein I were used for initial AgfA homology build-up procedures ultimately resulting in three structural models; beta barrel, beta prism and parallel beta helix. The beta barrel model is a compact, albeit irregular structure, with the beta strands arranged in two antiparallel beta sheet faces. The beta prism model does not reflect the 5 or 10-fold symmetry of the AgfA primary sequence. However, the favored, parallel beta helix model is a compact coil of ten helically arranged beta strands forming two parallel beta sheet faces. This arrangement predicts a regular, potentially stable, C-terminal core region consistent with the observed tandem repeat sequences, protease-resistance and strong tendency of this fimbrin to oligomerize and aggregate. Positional conservation of amino acid residues in AgfA and the Escherichia coli AgfA homologue, CsgA, provides strong support for this model. The parallel beta helix model of AgfA offers an interesting solution to a multifunctional fimbrin molecular surface having solvent exposed areas, regions for major and minor subunit interactions as well as fiber-fiber interactions common to many bacterial fimbriae. (C) 1999 Academic Press.