Lipid-restricted recognition of mycobacterial lipoglycans by human pulmonary surfactant protein A: a surface-plasmon-resonance study.
The human pulmonary surfactant protein A (hSP-A), a member of the mammalian collectin family, is thought to play a key defensive role against airborne invading pulmonary pathogens, among which is Mycobacterium tuberculosis, the aetiologic agent of tuberculosis. hSP-A has been shown to promote the uptake and the phagocytosis of pathogenic bacilli through the recognition and the binding of carbohydrate motifs on the invading pathogen surface. Recently we identified lipomannan and mannosylated lipoarabinomannan (ManLAM), two major mycobacterial cell-wall lipoglycans, as potential ligands for binding of hSP-A. We demonstrated that both the terminal mannose residues and the fatty acids are critical for binding, whereas the inner arabinosyl and mannosyl domains do not participate. In the present study we developed a surface-plasmon-resonance assay to analyse the molecular basis for the recognition of ManLAM by hSP-A and to try to define further the role of the lipidic aglycone moiety. Binding of ManLAM to immobilized hSP-A was consistent with the simplest one-to-one interaction model involving a single class of carbohydrate-binding site. This observation strongly suggests that the lipid moiety of ManLAM does not directly interact with hSP-A, but is rather responsible for the macromolecular organization of the lipoglycan, which may be necessary for efficient recognition of the terminal mannosyl epitopes. The indirect, structural role of the lipoglycan lipidic component is further supported by the complete lack of interaction with hSP-A in the presence of a low concentration of mild detergent.
Sidobre
Stéphane
S
Institut de Pharmacologie et de Biologie Structurale du CNRS, 205 route de Narbonne, 31077 Toulouse Cedex, France.
Puzo
Germain
G
Rivière
Michel
M
D001665:Binding Sites; D002240:Carbohydrate Sequence; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000737:chemistry*; D011510:Proteolipids / Q000378:metabolism*; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism*; D020349:Surface Plasmon Resonance
D008024:Ligands; D008055:Lipids; D008070:Lipopolysaccharides; D011510:Proteolipids; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants