Structural insights into antibody recognition of mycobacterial polysaccharides

J Mol Biol. 2009 Sep 18;392(2):381-92. doi: 10.1016/j.jmb.2009.06.074. Epub 2009 Jul 3.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Bacterial / chemistry*
  • Antibodies, Bacterial / immunology
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology
  • Carbohydrate Sequence
  • Crystallography, X-Ray
  • Lipopolysaccharides / chemistry*
  • Lipopolysaccharides / immunology
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Mycobacterium / chemistry*
  • Mycobacterium / immunology
  • Polysaccharides, Bacterial / chemistry*
  • Polysaccharides, Bacterial / immunology
  • Protein Binding
  • Protein Structure, Tertiary


  • Antibodies, Bacterial
  • Antibodies, Monoclonal
  • Lipopolysaccharides
  • Polysaccharides, Bacterial
  • lipoarabinomannan

Associated data

  • PDB/3HNS
  • PDB/3HNT
  • PDB/3HNV