Crystal structure of the V-region of Streptococcus mutans antigen I/II at 2.4 A resolution suggests a sugar preformed binding site.
Antigens I/II are large multifunctional adhesins from oral viridans streptococci that exert immunomodulatory effects on human cells and play important roles in inflammatory disorders. Among them, Streptococcus mutans plays a major role in the initiation of dental caries. The structure of the V-region (SrV+, residues 464-840) of the antigen I/II of S. mutans has been determined using the multiwavelength anomalous diffraction phasing technique with seleno-methionine-substituted recombinant protein and subsequently refined at 2.4 A resolution. The crystal structure of SrV+ revealed a lectin-like fold that displays a putative preformed carbohydrate-binding site stabilized by a metal ion. Inhibition of this binding site may confer to humans a protection against dental caries and dissemination of the bacteria to extra-oral sites involved in life-threatening inflammatory diseases. This crystal structure constitutes a first step in understanding the structure-function relationship of antigens I/II and may help in delineating new preventive or therapeutic strategies against colonization of the host by oral streptococci.
Troffer-Charlier
Nathalie
N
Institut National de la Santé et de la Recherche Médicale U424, Faculté de Chirurgie Dentaire, Université Louis Pasteur, 11 rue Humann, 67085 Strasbourg, France.
Ogier
Joëlle
J
Moras
Dino
D
Cavarelli
Jean
J
D018829:Adhesins, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D003460:Crystallization; D004926:Escherichia coli / Q000235:genetics; D008562:Membrane Glycoproteins; D008958:Models, Molecular; D011392:Proline / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification; D020539:Sequence Analysis, Protein; D012964:Sodium / Q000737:chemistry; D013295:Streptococcus mutans / Q000276:immunology*; D014867:Water / Q000737:chemistry
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; C055764:S-layer proteins; D014867:Water; D011392:Proline; D012964:Sodium