Elongated fibrillar structure of a streptococcal adhesin assembled by the high-affinity association of alpha- 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 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.
Department of Physiology and Biophysics, University of Alabama, Birmingham, AL 35294, USA.
Matthew R
MR
Larson
Kanagalaghatta R
KR
Rajashankar
Manisha H
MH
Patel
Rebekah A
RA
Robinette
Paula J
PJ
Crowley
Suzanne
S
Michalek
L Jeannine
LJ
Brady
Champion
C
Deivanayagam
D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000235:genetics; D000595:Amino Acid Sequence; D001667:Binding, Competitive; D002151:Calorimetry; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D013295:Streptococcus mutans / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D020349:Surface Plasmon Resonance
D018829:Adhesins, Bacterial; D010446:Peptide Fragments; D011994:Recombinant Proteins