Crystal Structure of the C-terminal Region of Streptococcus mutans Antigen I/II and Characterization of Salivary Agglutinin Adherence Domains

TY - JOUR

T1 - Crystal Structure of the C-terminal Region of Streptococcus mutans Antigen I/II and Characterization of Salivary Agglutinin Adherence Domains

AU - Larson, Matthew R.

AU - Rajashankar, Kanagalaghatta R.

AU - Crowley, Paula J.

AU - Kelly, Charles

AU - Mitchell, Tim J.

AU - Brady, L. Jeannine

AU - Deivanayagam, Champion

PY - 2011/6/17

Y1 - 2011/6/17

N2 - The Streptococcus mutans antigen I/II (AgI/II) is a cell surface-localized protein that adheres to salivary components and extracellular matrix molecules. Here we report the 2.5 angstrom resolution crystal structure of the complete C-terminal region of AgI/II. The C-terminal region is comprised of three major domains: C-1, C-2, and C-3. Each domain adopts a DE-variant IgG fold, with two beta-sheets whose A and F strands are linked through an intramolecular isopeptide bond. The adherence of the C-terminal AgI/II fragments to the putative tooth surface receptor salivary agglutinin (SAG), as monitored by surface plasmon resonance, indicated that the minimal region of binding was contained within the first and second DE-variant-IgG domains (C1 and C2) of the C terminus. The minimal C-terminal region that could inhibit S. mutans adherence to SAG was also confirmed to be within the C-1 and C-2 domains. Competition experiments demonstrated that the C-and N-terminal regions of AgI/II adhere to distinct sites on SAG. A cleft formed at the intersection between these C-1 and C-2 domains bound glucose molecules from the cryo-protectant solution, revealing a putative binding site for its highly glycosylated receptor SAG. Finally, electron microscopy images confirmed the elongated structure of AgI/II and enabled building a composite tertiary model that encompasses its two distinct binding regions.

AB - The Streptococcus mutans antigen I/II (AgI/II) is a cell surface-localized protein that adheres to salivary components and extracellular matrix molecules. Here we report the 2.5 angstrom resolution crystal structure of the complete C-terminal region of AgI/II. The C-terminal region is comprised of three major domains: C-1, C-2, and C-3. Each domain adopts a DE-variant IgG fold, with two beta-sheets whose A and F strands are linked through an intramolecular isopeptide bond. The adherence of the C-terminal AgI/II fragments to the putative tooth surface receptor salivary agglutinin (SAG), as monitored by surface plasmon resonance, indicated that the minimal region of binding was contained within the first and second DE-variant-IgG domains (C1 and C2) of the C terminus. The minimal C-terminal region that could inhibit S. mutans adherence to SAG was also confirmed to be within the C-1 and C-2 domains. Competition experiments demonstrated that the C-and N-terminal regions of AgI/II adhere to distinct sites on SAG. A cleft formed at the intersection between these C-1 and C-2 domains bound glucose molecules from the cryo-protectant solution, revealing a putative binding site for its highly glycosylated receptor SAG. Finally, electron microscopy images confirmed the elongated structure of AgI/II and enabled building a composite tertiary model that encompasses its two distinct binding regions.

U2 - 10.1074/jbc.M111.231100

DO - 10.1074/jbc.M111.231100

M3 - Article

SN - 1083-351X

VL - 286

SP - 21657

EP - 21666

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 24

ER -