Koretke Kristin K, Szczesny Pawel, Gruber Markus, Lupas Andrei N
Protein Bioinformatics Group, GlaxoSmithKline, Collegeville, PA 19426-0989, USA.
J Struct Biol. 2006 Aug;155(2):154-61. doi: 10.1016/j.jsb.2006.03.012. Epub 2006 Apr 3.
Non-fimbrial adhesins, such as Yersinia YadA, Moraxella UspA1 and A2, Haemophilus Hia and Hsf, or Bartonella BadA represent an important class of molecules by which pathogenic proteobacteria adhere to their hosts. They form trimeric surface structures with a head-stalk-anchor architecture. Whereas head and stalk domains are diverse and appear (frequently repetitively) in different combinations, the anchor domains are homologous and display the properties of autotransporters. We have built a molecular model for the prototypical non-fimbrial adhesin, YadA, by combining the crystal structure of the head (PDB:1P9H) with theoretical models for the stalk and the anchor. The head domain is a single-stranded, left-handed beta-helix, connected to the stalk by a conserved trimerization element (the neck). The stalk consists of a right-handed coiled coil, containing ten 15-residue repeats with a C-terminal stutter (insertion of four residues). The stalk continues into the conserved anchor domain, which is formed by four heptads of a left-handed coiled coil, followed by four transmembrane beta-strands. Our model of the YadA coiled coil, generated with the program BeammotifCC, combines these periodicities into a structure that starts with a pronounced right-handed supercoil and ends with a canonical, left-handed conformation. The last two heptads of the coiled coil are located within a 12-stranded beta-barrel, formed by trimerization of the four transmembrane beta-strands in each monomer. We propose that this pore assembles in the outer membrane to form the opening through which the monomer chains exit the cell. After export is completed, the fiber folds and the pore is occluded by the coiled coil. Our model explains how these proteins can act as autotransporters in the absence of any homology to classical, single-chain autotransporters.
非菌毛黏附素，如耶尔森菌的YadA、莫拉克斯氏菌的UspA1和A2、流感嗜血杆菌的Hia和Hsf，或巴尔通体的BadA，是致病变形菌黏附宿主的一类重要分子。它们形成具有头-柄-锚结构的三聚体表面结构。头和柄结构域多样，且常以不同组合（常重复出现）呈现，而锚定结构域是同源的，具有自转运蛋白的特性。我们通过将头部的晶体结构（PDB:1P9H）与柄和锚定的理论模型相结合，构建了典型非菌毛黏附素YadA的分子模型。头部结构域是单链左手β-螺旋，通过保守的三聚化元件（颈部）与柄相连。柄由右手卷曲螺旋组成，包含十个15个残基的重复序列以及一个C端口吃（插入四个残基）。柄延续到保守的锚定结构域，该结构域由左手卷曲螺旋的四个七肽组成，随后是四个跨膜β-链。我们用BeammotifCC程序生成的YadA卷曲螺旋模型，将这些周期性结构组合成一个结构，该结构起始于明显的右手超螺旋，结束于典型的左手构象。卷曲螺旋的最后两个七肽位于一个12链β-桶内，该β-桶由每个单体中四个跨膜β-链的三聚化形成。我们认为这个孔在外膜中组装形成单体链离开细胞的开口。输出完成后，纤维折叠，孔被卷曲螺旋封闭。我们的模型解释了这些蛋白质在与经典单链自转运蛋白无任何同源性的情况下如何充当自转运蛋白。
