Department of Structural Biology, Institut de Biologia Molecular de Barcelona (IBMB-CSIC), Parc Científic de Barcelona, Baldiri Reixac 10-12, 08028 Barcelona, Spain.
Acta Crystallogr F Struct Biol Commun. 2020 Nov 1;76(Pt 11):508-516. doi: 10.1107/S2053230X20012297. Epub 2020 Oct 8.
The human pathogen Mycoplasma genitalium is responsible for urethritis in men, and for cervicitis and pelvic inflammatory disease in women. The adherence of M. genitalium to host target epithelial cells is mediated through an adhesion complex called Nap, which is essential for infectivity. Nap is a transmembrane dimer of heterodimers of the immunodominant proteins P110 and P140. The M. genitalium genome contains multiple copies of portions that share homology with the extracellular regions of P140 and P110 encoded by the genes mg191 and mg192, respectively. Homologous recombination between the genes and the copies allows the generation of a large diversity of P140 and P110 variants to overcome surveillance by the host immune system. Interestingly, the C-terminal domain (C-domain) of the extracellular region of P140, which is essential for the function of Nap by acting as a flexible stalk anchoring the protein to the mycoplasma membrane, presents a low degree of sequence variability. In the present work, the X-ray crystal structures of two crystal forms of a construct of the P140 C-domain are reported. In both crystal forms, the construct forms a compact octamer with D4 point-group symmetry. The structure of the C-domain determined in this work presents significant differences with respect to the structure of the C-domain found recently in intact P140. The structural plasticity of the C-domain appears to be a possible mechanism that may help in the functioning of the mycoplasma adhesion complex.
人类病原体支原体生殖器是男性尿道炎的原因,也是女性宫颈炎和盆腔炎的原因。支原体生殖器对宿主靶上皮细胞的附着是通过一种称为 Nap 的粘附复合物介导的,该复合物对感染性至关重要。Nap 是免疫显性蛋白 P110 和 P140 的异二聚体的跨膜二聚体。支原体生殖器基因组包含多个与基因 mg191 和 mg192 编码的 P140 和 P110 的细胞外区域同源的部分的拷贝,分别。基因和拷贝之间的同源重组允许产生大量的 P140 和 P110 变体,以克服宿主免疫系统的监测。有趣的是,P140 细胞外区域的 C 末端结构域(C 结构域)对于 Nap 的功能至关重要,因为它作为一个灵活的茎将蛋白质锚定在支原体膜上,其序列变异性低。在本工作中,报道了 P140 C 结构域的两种晶体形式的构建体的 X 射线晶体结构。在两种晶体形式中,构建体形成具有 D4 点群对称性的紧凑八聚体。本工作确定的 C 结构域的结构与最近在完整 P140 中发现的 C 结构域的结构有显著差异。C 结构域的结构可塑性似乎是一种可能的机制,有助于支原体粘附复合物的功能。