Batchelor M, Prasannan S, Daniell S, Reece S, Connerton I, Bloomberg G, Dougan G, Frankel G, Matthews S
Department of Biochemistry and Centre for Structural Biology, Imperial College of Science, Technology and Medicine, London SW7 2AZ, UK.
EMBO J. 2000 Jun 1;19(11):2452-64. doi: 10.1093/emboj/19.11.2452.
Intimin is a bacterial adhesion molecule involved in intimate attachment of enteropathogenic and enterohaemorrhagic Escherichia coli to mammalian host cells. Intimin targets the translocated intimin receptor (Tir), which is exported by the bacteria and integrated into the host cell plasma membrane. In this study we localized the Tir-binding region of intimin to the C-terminal 190 amino acids (Int190). We have also determined the region's high-resolution solution structure, which comprises an immunoglobulin domain that is intimately coupled to a novel C-type lectin domain. This fragment, which is necessary and sufficient for Tir interaction, defines a new super domain in intimin that exhibits striking structural similarity to the integrin-binding domain of the Yersinia invasin and C-type lectin families. The extracellular portion of intimin comprises an articulated rod of immunoglobulin domains extending from the bacterium surface, conveying a highly accessible 'adhesive tip' to the target cell. The interpretation of NMR-titration and mutagenesis data has enabled us to identify, for the first time, the binding site for Tir, which is located at the extremity of the Int190 moiety.
紧密素是一种细菌粘附分子，参与肠道致病性大肠杆菌和肠出血性大肠杆菌与哺乳动物宿主细胞的紧密附着。紧密素作用于易位紧密素受体（Tir），Tir由细菌分泌并整合到宿主细胞质膜中。在本研究中，我们将紧密素的Tir结合区域定位到C端的190个氨基酸（Int190）。我们还确定了该区域的高分辨率溶液结构，其包含一个与新型C型凝集素结构域紧密相连的免疫球蛋白结构域。这个片段对于Tir相互作用是必需且充分的，它在紧密素中定义了一个新的超结构域，该超结构域与耶尔森氏菌侵袭素的整合素结合结构域和C型凝集素家族具有惊人的结构相似性。紧密素的细胞外部分包括从细菌表面延伸的免疫球蛋白结构域的铰接杆，将一个极易接近的“粘附尖端”传递给靶细胞。对核磁共振滴定和诱变数据的解释使我们首次确定了Tir的结合位点，该位点位于Int190部分的末端。
