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

Academic Article

Abstract

  • 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 A) crystal structure of the A(3)VP(1) fragment of S. mutans AgI/II that demonstrates a unique fibrillar form (155 A) 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 A(3) and P(1) 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.
  • Keywords

  • Adhesins, Bacterial, Amino Acid Sequence, Binding, Competitive, Calorimetry, Crystallography, X-Ray, Models, Molecular, Molecular Sequence Data, Peptide Fragments, Protein Structure, Secondary, Recombinant Proteins, Repetitive Sequences, Amino Acid, Sequence Homology, Amino Acid, Streptococcus mutans, Surface Plasmon Resonance
  • Digital Object Identifier (doi)

    Author List

  • Larson MR; Rajashankar KR; Patel MH; Robinette RA; Crowley PJ; Michalek S; Brady LJ; Deivanayagam C
  • Start Page

  • 5983
  • End Page

  • 5988
  • Volume

  • 107
  • Issue

  • 13