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 underlyi...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2010-08, Vol.107 (13), p.5983
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:
AGGLUTININS
ANTIGENS
ARCHITECTURE
Binding sites
CALORIMETRY
CRYSTAL STRUCTURE
MATERIALS SCIENCE
PLASMONS
PROTEIN STRUCTURE
PROTEINS
RESONANCE
SEDIMENTATION
STREPTOCOCCUS
Streptococcus infections
TITRATION
VELOCITY
VIRULENCE
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Summary: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...VP... 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... repeat of the alanine-rich domain adopts an extended α-helix that intertwines with the P... 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... and P... 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. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0912293107