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PDBsum entry 3hns
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Immune system
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PDB id
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3hns
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References listed in PDB file
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Key reference
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Title
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Structural insights into antibody recognition of mycobacterial polysaccharides.
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Authors
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T.Murase,
R.B.Zheng,
M.Joe,
Y.Bai,
S.L.Marcus,
T.L.Lowary,
K.K.Ng.
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Ref.
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J Mol Biol, 2009,
392,
381-392.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 1.
Fig. 1. Non-reducing arabinan motifs in LAM (compounds 1 and
2) and oligosaccharides 3−5.
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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.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2009,
392,
381-392)
copyright 2009.
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