pH Dependent Proteolysis of Neural Cadherin

Walters, Candice Ashton (2013) pH Dependent Proteolysis of Neural Cadherin. Undergraduate thesis, under the direction of Susan Pedigo from Chemistry and Biochemistry, University of Mississippi.

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Abstract

Cadherins are the primary calcium-dependent cell-cell adhesion molecule and are essential to vertebrates. They ensure the integrity of epithelial barriers that allow for maintenance of homeostasis in humans and protection against invading microorganisms. A common invader capable of forging past this line of defense is the fungus Candida albicans. The main virulence mechanism of C. alibans in acidic environments is its secreted aspartyl proteinases (SAPs), which are hydrolytic enzymes that degrade cadherin-mediated cell adhesion leading to infection of the underlying tissues. Cadherin is normally resistant to cleavage by proteases due to stabilization of the protein structure by bound calcium and the high levels of calcium in the extracellular space. The binding of calcium to cadherin requires intact, functional calcium binding sites comprising clusters of carbonyls and negatively charged carboxylates. Thus, there are two main environmental factors that contribute to the ability of the SAPs to degrade cadherins in vivo: low pH protonates acidic carboxylates in the calcium binding sites, thereby decreasing the calcium binding affinity, and the dysregulated calcium concentration in the acidic lumen of the host tissue. This thesis investigates the pH and pCa dependence of protease susceptibility of Neural-cadherin (N-cadherin). The model protease used here is Endoproteinase Glu-C. As predicted, we observed an increase in susceptibility with a decrease in pH and an increase in pCa. There is one stable fragment that is formed after exposure to the protease with an apparent size of ~10,000 D based on migration in SDS-PAGE. Scanning the sequence of N-cadherin identified possible cleavage sites. Future studies will reveal the identity of this stable fragment.

Item Type: Thesis (Undergraduate)
Creators: Walters, Candice Ashton
Student's Degree Program(s): B.A. in Biochemistry
Thesis Advisor: Susan Pedigo
Thesis Advisor's Department: Chemistry and Biochemistry
Institution: University of Mississippi
Subjects: Q Science > QD Chemistry
Depositing User: Ashton Walters
Date Deposited: 31 Jul 2014 14:38
Last Modified: 23 Oct 2015 19:16
URI: http://thesis.honors.olemiss.edu/id/eprint/238

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