Elongated fibrillar structure of a streptococcal adhesin assembled by the high-affinity association of α- and PPII-helices

Streptococcus mutans antigen I/II (AgI/II) is a cell surface-localized protein adhesin that interacts with salivary components within the salivary pellicle. AgI/II contributes to virulence and has been studied as an immunological and structural target, but a fundamental understanding of its underlying architecture has been lacking. Here we report a high-resolution (1.8 angstrom) crystal structure of the A(3)VP(1) fragment of S. mutans AgI/II that demonstrates a unique fibrillar form (155 angstrom) through the interaction of two noncontiguous regions in the primary sequence. The A(3) repeat of the alanine-rich domain adopts an extended alpha-helix that intertwines with the P-1 repeat polyproline type II (PPII) helix to form a highly extended stalk-like structure heretofore unseen in prokaryotic or eukaryotic protein structures. Velocity sedimentation studies indicate that full-length AgI/II that contains three A/P repeats extends over 50 nanometers in length. Isothermal titration calorimetry revealed that the high-affinity association between the A3 and P1 helices is enthalpically driven. Two distinct binding sites on AgI/ II to the host receptor salivary agglutinin (SAG) were identified by surface plasmon resonance (SPR). The current crystal structure reveals that AgI/ II family proteins are extended fibrillar structures with the number of alanine-and proline-rich repeats determining their length.