Dissertation/Thesis Abstract

Elucidation of the elongated fibrillar structure of Streptococcus mutans antigen I/II
by Larson, Matthew Rodney, Ph.D., The University of Alabama at Birmingham, 2011, 133; 3457162
Abstract (Summary)

Streptococcus mutans (S. mutans) is the causative agent behind dental caries, an infectious disease also known as tooth decay or dental cavities. S. mutans has a cell wall-attached protein known as Antigen I/II (AgI/II) utilized for bacterial adhesion to the tooth surface. Here we have solved the structures of both amino- and carboxy-terminal regions of the AgI/II molecule using X-ray crystallography. Using this structural information we have now built a tertiary model for AgI/II as a fibrillar protein. Further, we have functionally characterized AgI/II and determined minimal regions of AgI/II that are implicated in its adherence to the salivary agglutinin found on the tooth surface.

The following results are presented in this thesis work: (1) We report the high resolution structure (1.8 Å) of an amino-terminal fragment of AgI/II. This fragment reveals that AgI/II is an elongated molecule with a stalk comprised of α- and polyproline type-II (PPII)-helices. The hybrid structure formed from α- and PPII helices represents the first example of a new structural class of fibrillar proteins. (2) We report the (2.5 Å) crystal structure of the complete carboxy-terminus of AgI/II. This structure now shows that the AgI/II carboxy-terminus has three domains that each each adopt the DE-variant immunoglobulin-like fold. (3) Using the amino- and carboxy- terminal structures of AgI/II, biophysical characterizations, and electron microscopic imaging, we have now created an overall tertiary model for AgI/II family of proteins. (4) Adherence studies for AgI/II revealed that AgI/II contains two distinct regions that adhered to human salivary agglutinin (SAG). These regions of AgI/II also adhered non-competitively to SAG. These results now suggest possible models for the S. mutans bacterial adherence to SAG.

AgI/II can now be described as an elongated fibrillar protein with globular domains at its termini. The V-region is distal to the cell surface, while three carboxy-terminal domains are close to the cell surface. These globular regions are separated by the alanine-rich and proline-rich repeats of AgI/II that form a unique α- and PPII helical hybrid fibril which is revealed for the first time by these structures. This research now provides the first overall structural model for AgI/II as a fibrillar protein.

Keywords: Streptococcus mutans, Antigen I/II, fibrillar, structure

Indexing (document details)
Advisor: Deivanayagam, Champion
Commitee: DeLucas, Lawrence, Fuller, Catherine, Michalek, Suzanne, Smith, Peter
School: The University of Alabama at Birmingham
Department: Cellular and Molecular Physiology
School Location: United States -- Alabama
Source: DAI-B 72/08, Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Microbiology, Biochemistry, Biophysics
Keywords: Adhesin, Antigen I/II, Crystallography, Fibrillar structure, Streptococcus mutans
Publication Number: 3457162
ISBN: 9781124672281
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