PDBsum entry: 1yck

Immune system

PDB id: 1yck

Contents

Protein chain

167 a.a. *

Waters ×200

* Residue conservation analysis

PDB id:

1yck

Name:

Immune system

Title:

Crystal structure of human peptidoglycan recognition protein (pgrp-s)

Structure:

Peptidoglycan recognition protein. Chain: a. Synonym: peptidoglycan recognition protein s, sbbi68, pgrp- s, unq639/pro1269. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.70Å R-factor: 0.183 R-free: 0.210

Authors:

R.Guan,Q.Wang,E.J.Sundberg,R.A.Mariuzza

Key ref:

R.Guan et al. (2005). Crystal structure of human peptidoglycan recognition protein S (PGRP-S) at 1.70 A resolution. J Mol Biol, 347, 683-691. PubMed id: 15769462 DOI: 10.1016/j.jmb.2005.01.070

Date:

22-Dec-04 Release date: 22-Mar-05

Protein chain

O75594  (PGRP1_HUMAN) -  Peptidoglycan recognition protein 1

Seq: 196 a.a.

Struc: 167 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (1 term)
• Biological process: immune response (7 terms)
• Biochemical function: protein binding (5 terms)

DOI no: 10.1016/j.jmb.2005.01.070

J Mol Biol 347:683-691 (2005)

PubMed id: 15769462

Crystal structure of human peptidoglycan recognition protein S (PGRP-S) at 1.70 A resolution.

R.Guan, Q.Wang, E.J.Sundberg, R.A.Mariuzza.

ABSTRACT

Peptidoglycan recognition proteins (PGRPs) are pattern recognition receptors of the innate immune system that bind peptidoglycans (PGNs) of bacterial cell walls. These molecules, which are highly conserved from insects to mammals, contribute to host defense against infections by both Gram-positive and Gram-negative bacteria. Here, we present the crystal structure of human PGRP-S at 1.70A resolution. The overall structure of PGRP-S, which participates in intracellular killing of Gram-positive bacteria, is similar to that of other PGRPs, including Drosophila PGRP-LB and PGRP-SA and human PGRP-Ialpha. However, comparison with these PGRPs reveals important differences in both the PGN-binding site and a groove formed by the PGRP-specific segment on the opposite face of the molecule. This groove, which may constitute a binding site for effector or signaling proteins, is less hydrophobic and deeper in PGRP-S than in PGRP-IalphaC, whose PGRP-specific segments vary considerably in amino acid sequence. By docking a PGN ligand into the PGN-binding cleft of PGRP-S based on the known structure of a PGRP-Ialpha-PGN complex, we identified potential PGN-binding residues in PGRP-S. Differences in PGN-contacting residues and interactions suggest that, although PGRPs may engage PGNs in a similar mode, structural differences exist that likely regulate the affinity and fine specificity of PGN recognition.

Selected figure(s)

Figure 1.
Figure 1. Ribbon diagrams of the crystal structure of human PGRP-S. (a) The view is looking down on the PGN-binding cleft, whose walls are formed by helix a1 and four loops (b3-a1, a1-b4, b5-b6 and b7-a3) extending above the b-sheet platform. Secondary structure elements are labeled following the numbering for human PGRP-Ia.32 The N and C termini are indicated. The N-terminal PGRP-specific segment is shown in yellow. Disulfide bonds are purple. (b) View of the opposite face of the PGRP domain from that in (a), looking down onto the PGRP-specific segment. The molecule was rotated 220° about a vertical axis and 20° about a horizontal axis compared to the orientation in (a). The Figures were prepared with MOLSCRIPT36 and rendered by Raster3D.37

Figure 2.
Figure 2. PGN-binding site and possible PGN-contacting residues of human PGRP-S. (a) Surface representation of the PGN-binding cleft of PGRP-S. The molecular surface is colored according to percentage identities of residues lining the PGN-binding cleft of PGRPs, based on alignments of 45 insect and mammalian sequences:33 red, >80% identical; purple, 60-80%; yellow, 40-60%; and green, <40%. The PGN analog MTP, which was docked into the PGN binding site of PGRP-S using the PRGP-IaC-MTP structure, is shown in ball-and-stick representation. Carbon atoms are cyan, nitrogen atoms dark blue, and oxygen atoms red. A putative binding pocket for the GlcNAc moiety of natural PGNs, not present in the MTP fragment, is circled in yellow. MTP was docked into PGRP-S by superposing PGRP-IaC onto PGRP-S and then manually positioning MTP into the binding cleft of the latter; no steric clashes were observed between MTP and binding site residues. The manually docked PGRP-S-MTP model was subjected to 200 cycles of energy minimization in CNS version 1.1.38 During minimization, the MTP ligand was free to move, MTP-contacting residues were restrained, and all other residues were fixed. The Figure was prepared with PyMOL (http://www.pymol.org). ALA, l-alanine; IDG, d-isoglutamine; LYS, l-lysine. (b) Potential interactions between PGRP-S and MTP in the docked model. MTP is cyan, PGRP-S is yellow, and contacting residues are green or purple. The orientation is the same as in (a). Hydrogen bonds are drawn as broken lines; residues predicted to form multiple van der Waals contacts are also shown. (c) Interactions between PGRP-IaC and MTP in the PGRP-IaC-MTP crystal structure.33 (d) Potential interactions between Drosophila PGRP-SA and MTeP (MurNAc-l-Ala-d-isoGln-l-Lys-d-Ala). The PGN ligand was docked into PGRP-SA as described for (a). In purple are predicted MTeP-contacting residues Ser158 and His42, whose mutation to alanine abolishes the l,d-carboxypeptidase activity of PGRP-SA.31 (e) Structure-based alignment of residues lining the PGN-binding grooves of human PGRP-S, human PGRP-IaC and Drosophila PGRP-SA.30^, 31^ and 32 Binding site residues are highlighted with different colors according to their percentage identity as described in (a) (red, >80%; purple, 60-80%; yellow, 40-60%, and green, <40%); flanking sequences, included for reference only, are not colored. Triangles above the human PGRP-S sequence mark MTP-contacting residues in the PGRP-IaC-MTP crystal structure.33

The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 347, 683-691) copyright 2005.

Figures were selected by an automated process.