PDBsum entry: 1sk3

Immune system

PDB id: 1sk3

Contents

Protein chain

165 a.a. *

Ligands

SO4

Metals

_NI ×2

Waters ×11

* Residue conservation analysis

PDB id:

1sk3

Name:

Immune system

Title:

Crystal structure of thE C-terminal peptidoglycan-binding domain of human peptidoglycan recognition protein ialpha

Structure:

Peptidoglycan recognition protein i-alpha. Chain: a. Synonym: peptidoglycan recognition protein intermediate alpha, pgrp-i-alpha, pglyrpialpha. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pgrpia. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.80Å R-factor: 0.219 R-free: 0.253

Authors:

R.Guan,E.L.Malchiodi,W.Qian,P.Schuck,R.A.Mariuzza

Key ref:

R.Guan et al. (2004). Crystal structure of the C-terminal peptidoglycan-binding domain of human peptidoglycan recognition protein Ialpha. J Biol Chem, 279, 31873-31882. PubMed id: 15140887 DOI: 10.1074/jbc.M404920200

Date:

04-Mar-04 Release date: 13-Jul-04

Protein chain

Q96LB9  (PGRP3_HUMAN) -  Peptidoglycan recognition protein 3

Seq: 341 a.a.

Struc: 165 a.a.

 Gene Ontology (GO) functional annotation 

• Biological process: peptidoglycan catabolic process (1 term)
• Biochemical function: protein binding (2 terms)

DOI no: 10.1074/jbc.M404920200

J Biol Chem 279:31873-31882 (2004)

PubMed id: 15140887

Crystal structure of the C-terminal peptidoglycan-binding domain of human peptidoglycan recognition protein Ialpha.

R.Guan, E.L.Malchiodi, Q.Wang, P.Schuck, R.A.Mariuzza.

ABSTRACT

Peptidoglycan recognition proteins (PGRPs) are pattern recognition receptors of the innate immune system that bind, and in some cases hydrolyze, peptidoglycans (PGNs) on bacterial cell walls. These molecules, which are highly conserved from insects to mammals, participate in host defense against both Gram-positive and Gram-negative bacteria. We report the crystal structure of the C-terminal PGN-binding domain of human PGRP-Ialpha in two oligomeric states, monomer and dimer, to resolutions of 2.80 and 1.65 A, respectively. In contrast to PGRPs with PGN-lytic amidase activity, no zinc ion is present in the PGN-binding site of human PGRP-Ialpha. The structure reveals that PGRPs exhibit extensive topological variability in a large hydrophobic groove, located opposite the PGN-binding site, which may recognize host effector proteins or microbial ligands other than PGN. We also show that full-length PGRP-Ialpha comprises two tandem PGN-binding domains. These domains differ at most potential PGN-contacting positions, implying different fine specificities. Dimerization of PGRP-Ialpha, which occurs through three-dimensional domain swapping, is mediated by specific binding of sodium ions to a flexible hinge loop, stabilizing the conformation found in the dimer. We further demonstrate sodium-dependent dimerization of PGRP-Ialpha in solution, suggesting a possible mechanism for modulating PGRP activity through the formation of multivalent adducts.

Selected figure(s)

Figure 3.
FIG. 3. Structural variability in PGRP-specific segments. A, superposition of PGRP-specific segments of human PGRP-I C (purple) and Drosophila PGRP-LB (green). B, interactions of the conserved central region of the PGRP-specific segment (yellow) of human PGRP-I C with the main body of the PGRP domain. Carbon atoms are yellow or light blue, nitrogen atoms are dark blue, oxygen atoms are red, and sulfur atoms are purple. Residues Cys194 and Cys238 of PGRP-I form a disulfide bond (purple). C, interactions of the central region of the PGRP-specific segment (yellow) of Drosophila PGRP-LB with the PGRP domain.

Figure 4.
FIG. 4. Surface analysis of potential ligand-binding sites of PGRPs. A, molecular surface of human PGRP-I C showing the hydrophobic groove (outlined in yellow) formed by the PGRP-specific segment and the 2-helix. The protein is oriented similarity as in Fig. 1B. Hydrophobic regions are green; polar regions are red. Surface hydrophobicities were calculated with GRASP (50). A deep hydrophobic pocket and the protruding 5- 6 loop are labeled 1 and 2, respectively. B, molecular surface of Drosophila PGRP-LB with its putative ligand-binding groove outlined in yellow. The orientation is the same as in A.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 31873-31882) copyright 2004.

Figures were selected by an automated process.