Evdokimov A G, Tropea J E, Routzahn K M, Copeland T D, Waugh D S
Protein Engineering Section, Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, PO Box B, Frederick, MD 21702-1201, USA.
Acta Crystallogr D Biol Crystallogr. 2001 Jun;57(Pt 6):793-9. doi: 10.1107/s0907444901004875. Epub 2001 May 25.
Yersinia pestis, the causative agent of bubonic plague, injects effector proteins into the cytosol of mammalian cells that enable the bacterium to evade the immune response of the infected organism by interfering with eukaryotic signal transduction pathways. YopH is a modular effector composed of a C-terminal protein tyrosine phosphatase (PTPase) domain and a multifunctional N-terminal domain that not only orchestrates the secretion and translocation of YopH into eukaryotic cells but also binds tyrosine-phosphorylated target proteins to mediate substrate recognition. The crystal structure of the N-terminal domain of YopH (YopH(N); residues 1-130) has been determined at 2.0 A resolution. The amino-acid sequences that target YopH for secretion from the bacterium and translocation into eukaryotic cells form integral parts of this compactly folded domain. The structure of YopH(N) bears no resemblance to eukaryotic phosphotyrosine-binding domains, nor is it reminiscent of any known fold. Residues that have been implicated in phosphotyrosine-dependent protein binding are clustered together on one face of YopH(N), but the structure does not suggest a mechanism for protein-phosphotyrosine recognition.
鼠疫耶尔森菌是腺鼠疫的病原体，它将效应蛋白注入哺乳动物细胞的胞质溶胶中，通过干扰真核信号转导途径，使细菌能够逃避受感染生物体的免疫反应。YopH是一种模块化效应蛋白，由一个C端蛋白酪氨酸磷酸酶（PTPase）结构域和一个多功能N端结构域组成，该N端结构域不仅协调YopH向真核细胞的分泌和转运，还结合酪氨酸磷酸化的靶蛋白以介导底物识别。YopH的N端结构域（YopH(N)；第1至130位氨基酸残基）的晶体结构已在2.0埃分辨率下确定。将YopH从细菌分泌并转运到真核细胞中的氨基酸序列构成了这个紧密折叠结构域的组成部分。YopH(N)的结构与真核磷酸酪氨酸结合结构域没有相似之处，也没有让人联想到任何已知的折叠形式。与磷酸酪氨酸依赖性蛋白结合有关的残基聚集在YopH(N)的一个面上，但该结构并未提示蛋白-磷酸酪氨酸识别的机制。
