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Membrane protein, immune system, toxin PDB id
2f2l
Jmol
Contents
Protein chains
167 a.a. *
166 a.a. *
Ligands
NAG
HSQ
SO4 ×2
MLD
CIT
Waters ×195
* Residue conservation analysis
PDB id:
2f2l
Name: Membrane protein, immune system, toxin
Title: Crystal structure of tracheal cytotoxin (tct) bound to the e complex of peptidoglycan recognition proteins lca (pgrp-lca (pgrp-lcx)
Structure: Peptidoglycan-recognition protein-lc isoform lca. Chain: a. Fragment: extracellular domain (residues 355-520). Synonym: immune response deficient 7 protein. Engineered: yes. Peptidoglycan recognition protein-lc isoform lcx. Chain: x. Fragment: extracellular domain (residues 335-500). Engineered: yes
Source: Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: hi-5 insect cells.
Biol. unit: Dimer (from PQS)
Resolution:
2.10Å     R-factor:   0.169     R-free:   0.214
Authors: C.I.Chang,J.Deisenhofer
Key ref:
C.I.Chang et al. (2006). Structure of tracheal cytotoxin in complex with a heterodimeric pattern-recognition receptor. Science, 311, 1761-1764. PubMed id: 16556841 DOI: 10.1126/science.1123056
Date:
17-Nov-05     Release date:   04-Apr-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9GNK5  (PGPLC_DROME) -  Peptidoglycan-recognition protein LC
Seq:
Struc: 		 
Seq:
Struc: 		520 a.a.
167 a.a.*
Protein chain
Pfam   ArchSchema ?
Q9GNK5  (PGPLC_DROME) -  Peptidoglycan-recognition protein LC
Seq:
Struc: 		 
Seq:
Struc: 		520 a.a.
166 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure
* PDB and UniProt seqs differ at 103 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     peptidoglycan catabolic process   1 term 
  Biochemical function     N-acetylmuramoyl-L-alanine amidase activity     2 terms  

 

 
DOI no: 10.1126/science.1123056 Science 311:1761-1764 (2006)
PubMed id: 16556841  
 
 
Structure of tracheal cytotoxin in complex with a heterodimeric pattern-recognition receptor.
C.I.Chang, Y.Chelliah, D.Borek, D.Mengin-Lecreulx, J.Deisenhofer.
 
  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.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. Interaction of TCT with the PG-docking groove in the LCx ectodomain. TCT is shown as pink sticks, and the LCx ectodomain is in ribbon representation with side chains of the TCT-interacting residues shown as green sticks. Hydrogen-bonding interactions are shown in yellow and listed in table S2. Water molecules are shown as red spheres. 		Figure 4.
Fig. 4. The LCa ectodomain interface for GlcNAc-MurNAc(anhydro) moiety of TCT and the LCx ectodomain. (A) Interaction of the disaccharide moiety presented by the LCx ectodomain (green) with the LCa ectodomain (blue). (B) Superposition of the interface residues in the complexed (blue) and uncomplexed (gray; PDB code 1Z6I) LCa ectodomains showing induced-fit conformational change of the side chains shown as sticks.
 
  The above figures are reprinted by permission from the AAAs: Science (2006, 311, 1761-1764) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21372849 N.Basbous, F.Coste, P.Leone, R.Vincentelli, J.Royet, C.Kellenberger, and A.Roussel (2011).
The Drosophila peptidoglycan-recognition protein LF interacts with peptidoglycan-recognition protein LC to downregulate the Imd pathway.
  EMBO Rep, 12, 327-333.
PDB codes: 2xz4 2xz8
21117117 M.Lee, D.Hesek, I.M.Shah, A.G.Oliver, J.Dworkin, and S.Mobashery (2010).
Synthetic peptidoglycan motifs for germination of bacterial spores.
  Chembiochem, 11, 2525-2529.  
20122400 N.Paquette, M.Broemer, K.Aggarwal, L.Chen, M.Husson, D.Ertürk-Hasdemir, J.M.Reichhart, P.Meier, and N.Silverman (2010).
Caspase-mediated cleavage, IAP binding, and ubiquitination: linking three mechanisms crucial for Drosophila NF-kappaB signaling.
  Mol Cell, 37, 172-182.  
20382864 R.E.Lehotzky, C.L.Partch, S.Mukherjee, H.L.Cash, W.E.Goldman, K.H.Gardner, and L.V.Hooper (2010).
Molecular basis for peptidoglycan recognition by a bactericidal lectin.
  Proc Natl Acad Sci U S A, 107, 7722-7727.  
19237650 A.Pennartz, C.Généreux, C.Parquet, D.Mengin-Lecreulx, and B.Joris (2009).
Substrate-induced inactivation of the Escherichia coli AmiD N-acetylmuramoyl-L-alanine amidase highlights a new strategy to inhibit this class of enzyme.
  Antimicrob Agents Chemother, 53, 2991-2997.  
20457557 C.Hetru, and J.A.Hoffmann (2009).
NF-kappaB in the immune response of Drosophila.
  Cold Spring Harb Perspect Biol, 1, a000232.  
19416268 J.V.Troll, D.M.Adin, A.M.Wier, N.Paquette, N.Silverman, W.E.Goldman, F.J.Stadermann, E.V.Stabb, and M.J.McFall-Ngai (2009).
Peptidoglycan induces loss of a nuclear peptidoglycan recognition protein during host tissue development in a beneficial animal-bacterial symbiosis.
  Cell Microbiol, 11, 1114-1127.  
  19616762 R.E.Vance, R.R.Isberg, and D.A.Portnoy (2009).
Patterns of pathogenesis: discrimination of pathogenic and nonpathogenic microbes by the innate immune system.
  Cell Host Microbe, 6, 10-21.  
19662170 S.Meister, B.Agianian, F.Turlure, A.Relógio, I.Morlais, F.C.Kafatos, and G.K.Christophides (2009).
Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites.
  PLoS Pathog, 5, e1000542.  
19193639 Y.Dong, and G.Dimopoulos (2009).
Anopheles fibrinogen-related proteins provide expanded pattern recognition capacity against bacteria and malaria parasites.
  J Biol Chem, 284, 9835-9844.  
19692333 Y.Mishima, J.Quintin, V.Aimanianda, C.Kellenberger, F.Coste, C.Clavaud, C.Hetru, J.A.Hoffmann, J.P.Latgé, D.Ferrandon, and A.Roussel (2009).
The N-terminal domain of Drosophila Gram-negative binding protein 3 (GNBP3) defines a novel family of fungal pattern recognition receptors.
  J Biol Chem, 284, 28687-28697.
PDB code: 3ie4
  18474356 F.Maillet, V.Bischoff, C.Vignal, J.Hoffmann, and J.Royet (2008).
The Drosophila peptidoglycan recognition protein PGRP-LF blocks PGRP-LC and IMD/JNK pathway activation.
  Cell Host Microbe, 3, 293-303.  
18984160 I.M.Shah, M.H.Laaberki, D.L.Popham, and J.Dworkin (2008).
A eukaryotic-like Ser/Thr kinase signals bacteria to exit dormancy in response to peptidoglycan fragments.
  Cell, 135, 486-496.  
18700763 M.Suvorov, M.Lee, D.Hesek, B.Boggess, and S.Mobashery (2008).
Lytic transglycosylase MltB of Escherichia coli and its role in recycling of peptidoglycan strands of bacterial cell wall.
  J Am Chem Soc, 130, 11878-11879.  
  20485470 S.Govind (2008).
Innate immunity in Drosophila: Pathogens and pathways.
  Insect Sci, 15, 29-43.  
17201680 B.Lemaitre, and J.Hoffmann (2007).
The host defense of Drosophila melanogaster.
  Annu Rev Immunol, 25, 697-743.  
17948019 D.Ferrandon, J.L.Imler, C.Hetru, and J.A.Hoffmann (2007).
The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections.
  Nat Rev Immunol, 7, 862-874.  
17363965 J.Royet, and R.Dziarski (2007).
Peptidoglycan recognition proteins: pleiotropic sensors and effectors of antimicrobial defences.
  Nat Rev Microbiol, 5, 264-277.  
17409189 J.W.Park, C.H.Kim, J.H.Kim, B.R.Je, K.B.Roh, S.J.Kim, H.H.Lee, J.H.Ryu, J.H.Lim, B.H.Oh, W.J.Lee, N.C.Ha, and B.L.Lee (2007).
Clustering of peptidoglycan recognition protein-SA is required for sensing lysine-type peptidoglycan in insects.
  Proc Natl Acad Sci U S A, 104, 6602-6607.  
17275309 R.Guan, and R.A.Mariuzza (2007).
Peptidoglycan recognition proteins of the innate immune system.
  Trends Microbiol, 15, 127-134.  
17502600 S.Cho, Q.Wang, C.P.Swaminathan, D.Hesek, M.Lee, G.J.Boons, S.Mobashery, and R.A.Mariuzza (2007).
Structural insights into the bactericidal mechanism of human peptidoglycan recognition proteins.
  Proc Natl Acad Sci U S A, 104, 8761-8766.
PDB codes: 2eav 2eax
17805526 S.M.Zhang, Y.Zeng, and E.S.Loker (2007).
Characterization of immune genes from the schistosome host snail Biomphalaria glabrata that encode peptidoglycan recognition proteins and gram-negative bacteria binding protein.
  Immunogenetics, 59, 883-898.  
17987029 T.B.Sackton, B.P.Lazzaro, T.A.Schlenke, J.D.Evans, D.Hultmark, and A.G.Clark (2007).
Dynamic evolution of the innate immune system in Drosophila.
  Nat Genet, 39, 1461-1468.  
17215869 V.Garlatti, N.Belloy, L.Martin, M.Lacroix, M.Matsushita, Y.Endo, T.Fujita, J.C.Fontecilla-Camps, G.J.Arlaud, N.M.Thielens, and C.Gaboriaud (2007).
Structural insights into the innate immune recognition specificities of L- and H-ficolins.
  EMBO J, 26, 623-633.
PDB codes: 2j0g 2j0h 2j0y 2j1g 2j2p 2j3f 2j3g 2j3o 2j3u 2j5z 2j60 2j61 2j64
17069638 J.D.Evans, K.Aronstein, Y.P.Chen, C.Hetru, J.L.Imler, H.Jiang, M.Kanost, G.J.Thompson, Z.Zou, and D.Hultmark (2006).
Immune pathways and defence mechanisms in honey bees Apis mellifera.
  Insect Mol Biol, 15, 645-656.  
16894338 K.A.Cloud-Hansen, S.B.Peterson, E.V.Stabb, W.E.Goldman, M.J.McFall-Ngai, and J.Handelsman (2006).
Breaching the great wall: peptidoglycan and microbial interactions.
  Nat Rev Microbiol, 4, 710-716.  
16930467 R.Dziarski, and D.Gupta (2006).
The peptidoglycan recognition proteins (PGRPs).
  Genome Biol, 7, 232.  
17139146 S.Kurata (2006).
[Intra- and extracellular recognition of pathogens and activation of innate immunity]
  Yakugaku Zasshi, 126, 1213-1218.  
16767093 T.Kaneko, T.Yano, K.Aggarwal, J.H.Lim, K.Ueda, Y.Oshima, C.Peach, D.Erturk-Hasdemir, W.E.Goldman, B.H.Oh, S.Kurata, and N.Silverman (2006).
PGRP-LC and PGRP-LE have essential yet distinct functions in the drosophila immune response to monomeric DAP-type peptidoglycan.
  Nat Immunol, 7, 715-723.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.