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Science 311 (5768): 1761-1764

Copyright © 2006 by the American Association for the Advancement of Science

Structure of Tracheal Cytotoxin in Complex with a Heterodimeric Pattern-Recognition Receptor

Chung-I Chang,1,2 Yogarany Chelliah,1,2 Dominika Borek,2 Dominique Mengin-Lecreulx,3 Johann Deisenhofer1,2*

Abstract: 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.

1 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Road, Dallas, TX 75390–9050, USA.
2 Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Road, Dallas, TX 75390–9050, USA.
3 Institut de Biochimie et Biophysique Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Université de Paris-Sud, 91405 Orsay, France.

* To whom correspondence should be addressed. E-mail: johann.deisenhofer{at}utsouthwestern.edu

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