3HNT

CS-35 Fab complex with a linear, terminal oligoarabinofuranosyl tetrasaccharide from lipoarabinomannan

Summary for 3HNT

• Entry DOI: 10.2210/pdb3hnt/pdb
• Related: 3HNS 3HNV
• Descriptor: CS-35 Fab Heavy Chain, CS-35 Fab Light Chain, beta-D-arabinofuranose-(1-2)-alpha-D-arabinofuranose-(1-5)-alpha-D-arabinofuranose-(1-5)-methyl alpha-D-arabinofuranoside, ... (4 entities in total)
• Functional Keywords: antibody-carbohydrate complex, oligofuranoside, tuberculosis, immune system
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 2
• Total formula weight: 48082.49

Authors

Murase, T.,Zheng, R.B.,Joe, M.,Bai, Y.,Marcus, S.L.,Lowary, T.L.,Ng, K.K.S. (deposition date: 2009-06-01, release date: 2009-07-21, Last modification date: 2024-11-27)

Primary citation

Murase, T.,Zheng, R.B.,Joe, M.,Bai, Y.,Marcus, S.L.,Lowary, T.L.,Ng, K.K.
Structural insights into antibody recognition of mycobacterial polysaccharides.
J.Mol.Biol., 392:381-392, 2009

PubMed 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.

PubMed: 19577573
DOI: 10.1016/j.jmb.2009.06.074

Experimental method

X-RAY DIFFRACTION (1.8 Å)