Structure of the virulence-associated protein VapD from the intracellular pathogen Rhodococcus equi.
Structure of the virulence-associated protein VapD from the intracellular pathogen Rhodococcus equi.
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DOI：
10.1107/s1399004714012632
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Wilkinson AJ
中科院分区：
文献类型：
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作者：
Whittingham JL;Blagova EV;Finn CE;Luo H;Miranda-CasoLuengo R;Turkenburg JP;Leech AP;Walton PH;Murzin AG;Meijer WG;Wilkinson AJ
VapD是来自多宿主病原体马红球菌的一组高度同源的毒力相关蛋白之一。晶体结构揭示了具有新颖折叠和富含甘氨酸的“秃”表面的八链β-桶。 马红球菌是一种多宿主病原体，感染一系列动物以及免疫受损的人类。马和猪分离株携带毒力质粒，该质粒编码与R. equi转移内体成熟的正常过程，使细菌能够在肺泡巨噬细胞中存活和增殖。为进一步研究Vap蛋白的毒力功能，测定了VapD的晶体结构。VapD是通过多角度激光散射测定的单体。该结构揭示了一个椭圆形的，紧凑的八链β-桶，具有新的链拓扑结构和伪双重对称性，表明从祖先二聚体进化而来。表面缔合的辛基-β-d-葡糖苷分子可能提供功能的线索。圆二色光谱分析表明，β-桶结构之前的N-末端的天然无序区域。序列比较表明，其他质粒编码的毒力相关蛋白的核心折叠来自R。Equi菌株与VapD菌株相似。进一步表明，编码推定的R.马Vap-like蛋白存在于不同的细菌物种中。最后，根据VapD独特的结构特征及其与其他β桶蛋白的部分结构相似性，讨论了该结构的功能意义。
VapD is one of a set of highly homologous virulence-associated proteins from the multi-host pathogen Rhodococcus equi. The crystal structure reveals an eight-stranded β-barrel with a novel fold and a glycine rich ‘bald’ surface. Rhodococcus equi is a multi-host pathogen that infects a range of animals as well as immune-compromised humans. Equine and porcine isolates harbour a virulence plasmid encoding a homologous family of virulence-associated proteins associated with the capacity of R. equi to divert the normal processes of endosomal maturation, enabling bacterial survival and proliferation in alveolar macrophages. To provide a basis for probing the function of the Vap proteins in virulence, the crystal structure of VapD was determined. VapD is a monomer as determined by multi-angle laser light scattering. The structure reveals an elliptical, compact eight-stranded β-barrel with a novel strand topology and pseudo-twofold symmetry, suggesting evolution from an ancestral dimer. Surface-associated octyl-β-d-glucoside molecules may provide clues to function. Circular-dichroism spectroscopic analysis suggests that the β-barrel structure is preceded by a natively disordered region at the N-terminus. Sequence comparisons indicate that the core folds of the other plasmid-encoded virulence-associated proteins from R. equi strains are similar to that of VapD. It is further shown that sequences encoding putative R. equi Vap-like proteins occur in diverse bacterial species. Finally, the functional implications of the structure are discussed in the light of the unique structural features of VapD and its partial structural similarity to other β-barrel proteins.