PDBsum entry: 1twq

Immune system, membrane protein

PDB-id: 1twq

Asymmetric unit

Contents

Description

Header details

Header records

References

PROCHECK

Protein chain

165 a.a. *

Ligands

AMU-ALA-GMA-LYS-NH2

Metal ions

_NI

Waters ×48

* Residue conservation analysis

Tools

Clefts Calculation

Biological unit*, tetramer
(*as deduced by PQS)

PDB id:

1twq

Name:

Immune system, membrane protein

Title:

Crystal structure of thE C-terminal pgn-binding domain of human pgrp-ialpha in complex with pgn analog muramyl tripeptide

Structure:

Peptidoglycan recognition protein-i-alpha. Chain: a. Fragment: c-terminal domain. Synonym: peptidoglycan recognition protein intermediate alpha. Pgrp-i-alpha. Pglyrpialpha. Peptidoglycan recognition protein 3. Engineered: yes. Other_details: complexed with pgn fragment (amu)a(gma) k(nh2).

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pglyrp3. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: the muramyl tripeptide exists in all baterial peptidoglycans

Biological unit:

Tetramer (from PQS)

UniProt:

Q96LB9 (PGRP3_HUMAN)

Seq:

Struc:

Seq:

341 a.a.

Struc:

165 a.a.

Key:	PfamA domain
Secondary structure	CATH domain

Resolution:

2.30Å

R-factor:

0.222

R-free:

0.252

Authors:

R.Guan,A.Roychowdury,G.-A.Boons,R.A.Mariuzza

Key ref:

R.Guan et al. (2004). Structural basis for peptidoglycan binding by peptidoglycan recognition proteins.. Proc Natl Acad Sci U S A, 101, 17168-17173. [PubMed id: 15572450] [DOI: 10.1073/pnas.0407856101]

Date:

01-Jul-04

Release date:

14-Dec-04

Related entries:

1sk3
crystal structure of thE C-terminal pgn-binding domain of
human pgrp-ialpha (form i)
1sk4
crystal structure of thE C-terminal pgn-binding domain of
human pgrp-ialpha (form ii)

Quick_links

Procheck

Clefts

Surface

Key reference

DOI no: 10.1073/pnas.0407856101

Proc Natl Acad Sci U S A 101:17168-17173 (2004)

PubMed id: 15572450

Structural basis for peptidoglycan binding by peptidoglycan recognition proteins.

R.Guan, A.Roychowdhury, B.Ember, S.Kumar, G.J.Boons, R.A.Mariuzza.

ABSTRACT

Peptidoglycan (PGN) recognition proteins (PGRPs) are pattern-recognition receptors of the innate immune system that bind and, in some cases, hydrolyze bacterial PGNs. We determined the crystal structure, at 2.30-A resolution, of the C-terminal PGN-binding domain of human PGRP-Ialpha in complex with a muramyl tripeptide representing the core of lysine-type PGNs from Gram-positive bacteria. The peptide stem of the ligand is buried at the deep end of a long binding groove, with N-acetylmuramic acid situated in the middle of the groove, whose shallow end can accommodate a linked N-acetylglucosamine. Although most interactions are with the peptide, the glycan moiety also seems to be essential for specific recognition by PGRPs. Conservation of key PGN-contacting residues shows that all PGRPs employ this basic PGN-binding mode. The structure pinpoints variable residues that likely mediate discrimination between lysine- and diaminopimelic acid-type PGNs. We also propose a mechanism for PGN hydrolysis by Zn(2+)-containing PGRPs.

Selected figure(s)

Figure 1.
Fig. 1. Structure of Lys-type PGNs and of the PGRP-I -MTP complex. (A) The PGN fragment, highlighted in red, corresponds to the MTP ligand used to form the PGRP-I -MTP complex. Lys-type PGN peptides are usually crosslinked through a peptide bridge composed of 1-5 glycines. In parentheses is a D-alanine residue at peptide position 5 missing in PGNs from many bacteria. In Dap-type PGNs, L-lysine is replaced by meso-diaminopimelic acid, and the peptide stems are directly connected. (B) Structure of the PGRP-I -MTP complex. Helices are shown in red, strands in yellow, and coils in cyan. Disulfide bonds are shown in purple. The labeling of secondary structure elements follows the numbering for unbound PGRP-I in ref. 28. The N- and C-termini are indicated. The bound MTP is shown in ball-and-stick representation, with carbon atoms in green, nitrogen atoms in blue, and oxygen atoms in red. (C) [A]-weighted F[o] - F[c] electron density map for the MTP ligand. The contour level is 2 . NHAc, acetamide; AMU, MurNAc; Ala, L-alanine; IDG, D-isoglutamine; Lys, L-lysine.

Figure 3.
Fig. 3. Intermolecular contacts in the PGRP-I C-MTP complex. (A) Stereoview of interactions between PGRP-I C and MTP at the PGN-binding site. MTP is shown in purple, PGRP-I C in yellow, and contacting residues in green. Hydrogen bonds are shown as dashed lines; residues forming van der Waals contacts with MTP are also highlighted. (B) Schematic representation of interactions between MTP and PGRP-I C. MTP is shown in red; hydrogen bonds are shown as blue dashed lines. Residues making van der Waals contacts with MTP are indicated by arcs with spokes radiating toward the ligand moieties they contact. Only residues making two or more such contacts are shown. No water-mediated interactions were observed. AMU, MurNAc; IDG, D-isoglutamine.

Figures were selected by the author.