All ETDs from UAB

Advisory Committee Chair

Champion Deivanayagam

Advisory Committee Members

Lawrence Delucas

Catherine Fuller

Suzanne Michalek

Peter Smith

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


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 &alpha- and polyproline type-II (PPII)-helices. The hybrid structure formed from &alpha- 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 &alpha- 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.



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