PDBsum entry 3hns

Immune system

PDB id: 3hns

Contents

Protein chains

220 a.a. *

214 a.a. *

Ligands

AXR-BXY-BXY-BXX-BXY-BXX

Waters ×508

* Residue conservation analysis

PDB id:

3hns

Name:

Immune system

Title:

Cs-35 fab complex with oligoarabinofuranosyl hexasaccharide

Structure:

Cs-35 fab heavy chain. Chain: h. Fragment: heavy chain. Cs-35 fab light chain. Chain: l. Fragment: light chain

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Organism_taxid: 10090

Resolution:

2.00Å R-factor: 0.172 R-free: 0.217

Authors:

T.Murase,R.B.Zheng,M.Joe,Y.Bai,S.L.Marcus,T.L.Lowary,K.K.S.Ng

Key ref:

T.Murase et al. (2009). Structural insights into antibody recognition of mycobacterial polysaccharides. J Mol Biol, 392, 381-392. PubMed id: 19577573 DOI: 10.1016/j.jmb.2009.06.074

Date:

01-Jun-09 Release date: 21-Jul-09

Protein chain

No UniProt id for this chain

Struc: 220 a.a.

Protein chain

No UniProt id for this chain

Struc: 214 a.a.

DOI no: 10.1016/j.jmb.2009.06.074

J Mol Biol 392:381-392 (2009)

PubMed id: 19577573

Structural insights into antibody recognition of mycobacterial polysaccharides.

T.Murase, R.B.Zheng, M.Joe, Y.Bai, S.L.Marcus, T.L.Lowary, K.K.Ng.

ABSTRACT

Mycobacteria are major human pathogens responsible for such serious and widespread diseases as tuberculosis and leprosy. Among the evolutionary adaptations essential for pathogenicity in mycobacteria is a complex carbohydrate-rich cell-wall structure that contains as a major immunomodulatory molecule the polysaccharide lipoarabinomannan (LAM). We report here crystal structures of three fragments from the non-reducing termini of LAM in complex with a murine antibody Fab fragment (CS-35Fab). These structures reveal for the first time the three-dimensional structures of key components of LAM and the molecular basis of LAM recognition at between 1.8- and 2.0-A resolution. The antigen-binding site of CS-35Fab forms three binding pockets that show a high degree of complementarity to the reducing end, the branch point and one of the non-reducing ends of the Y-shaped hexasaccharide moiety found at most of the non-reducing termini of LAM. Structures of CS-35Fab bound to two additional tetrasaccharides confirm the general mode of binding seen in the hexasaccharide and indicate how different parts of LAM are recognized. Altogether, these structures provide a rational basis for understanding the overall architecture of LAM and identify the key elements of an epitope that may be exploited for the development of novel and more effective anti-mycobacterial vaccines. Moreover, this study represents the first high-resolution X-ray crystallographic investigation of oligofuranoside-protein recognition.

Selected figure(s)

Figure 1.
Fig. 1. Non-reducing arabinan motifs in LAM (compounds 1 and 2) and oligosaccharides 3−5.

Figure 2.
Fig. 2. Structures of the CS-35Fab CDRs. (a and b) Space-filling representations of CDRs H1 (magenta), H2 (orange), H3 (red), L1 (blue), L2 (cyan) and L3 (green) bound to compound 3 (yellow dots). (c) Sequences of the CS-35Fab CDRs, with asterisks denoting residues forming direct or water-mediated contacts with compound 3. Residue numbering follows the Kabat convention, as implemented in Abnum.^23 For reference, the normal sequential numbering of residues of CDR H2 and that of residues of CDR H3 are shown as white numbers against a black background below the Kabat numbering. The normal sequential numbering of residues in CDR H1 and that of residues in the light chain are identical with the Kabat numbering.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2009, 392, 381-392) copyright 2009.

Figures were selected by an automated process.