Chang Chung-I, Chelliah Yogarany, Borek Dominika, Mengin-Lecreulx Dominique, Deisenhofer Johann
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Road, Dallas, TX 75390-9050, USA.
Science. 2006 Mar 24;311(5768):1761-4. doi: 10.1126/science.1123056.
Tracheal cytotoxin (TCT), a naturally occurring fragment of Gram-negative peptidoglycan, is a potent elicitor of innate immune responses in Drosophila. It induces the heterodimerization of its recognition receptors, the peptidoglycan recognition proteins (PGRPs) LCa and LCx, which activates the immune deficiency pathway. The crystal structure at 2.1 angstrom resolution of TCT in complex with the ectodomains of PGRP-LCa and PGRP-LCx shows that TCT is bound to and presented by the LCx ectodomain for recognition by the LCa ectodomain; the latter lacks a canonical peptidoglycan-docking groove conserved in other PGRPs. The interface, revealed in atomic detail, between TCT and the receptor complex highlights the importance of the anhydro-containing disaccharide in bridging the two ectodomains together and the critical role of diaminopimelic acid as the specificity determinant for PGRP interaction.
气管细胞毒素（TCT）是革兰氏阴性肽聚糖的天然片段，是果蝇先天免疫反应的有效诱导剂。它诱导其识别受体肽聚糖识别蛋白（PGRPs）LCa和LCx的异源二聚化，从而激活免疫缺陷途径。TCT与PGRP-LCa和PGRP-LCx胞外域复合物的2.1埃分辨率晶体结构表明，TCT与LCx胞外域结合并由其呈递，以供LCa胞外域识别；后者缺乏其他PGRPs中保守的典型肽聚糖对接槽。TCT与受体复合物之间的原子细节界面突出了含脱水二糖在将两个胞外域连接在一起方面的重要性，以及二氨基庚二酸作为PGRP相互作用特异性决定因素的关键作用。
