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

• Published in: Proceedings of the National Academy of Sciences - PNAS 2010, Vol.107 (13), p.5983-5988
• Main Authors: Larson, Matthew R, Rajashankar, Kanagalaghatta R, Patel, Manisha H, Robinette, Rebekah A, Crowley, Paula J, Michalek, Suzanne, Brady, L. Jeannine, Deivanayagam, Champion
• Format: Article
• Language: English
• Subjects: adhesins; agglutinins; antigens; binding sites; calorimetry; crystal structure; Streptococcus mutans; surface plasmon resonance; titration; virulence
• ISSN: 0027-8424; 1091-6490

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 Å) crystal structure of the A₃VP₁ fragment of S. mutans AgI/II that demonstrates a unique fibrillar form (155 Å) through the interaction of two noncontiguous regions in the primary sequence. The A₃ repeat of the alanine-rich domain adopts an extended α-helix that intertwines with the P₁ 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.