Susan Pedigo
Associate Professor of Chemistry and Biochemistry
Phone Number: (662)915-5328
Email: spedigo@olemiss.edu
http://www.olemiss.edu/depts/chemistry/faculty/index.php?faculty_id=13

Key Words: Biochemistry, stability, calcium binding and dimerization of cadherins

Research Description: Calcium-dependent Assembly of Cadherins

Cadherins are transmembrane proteins that are responsible for communication between identical cells through calcium-dependent interactions. Members of this family are named according to the cell type in which they predominate. Type I or classical cadherins (e.g. E- and N-cadherins) have a common domain organization. The N-terminal extracellular region has 5 independently folded modular domains connected in series according to primary sequence (Figure 1A). These ectodomains are anchored to the cell surface by a transmembrane segment, and organized spatially on the cell surface by a cytoplasmic domain that is connected indirectly to the actin cytoskeleton by catenins. Cadherins on the same cell surface can self-associate into cis-dimers (lateral dimers). The basis of adhesion is interactions between identical cadherins on neighboring cell surfaces to form trans-dimers (adhesive dimers; see Figure 1B). In spite of concerted effort by many research teams, there is still ambiguity about the structural nature of the lateral and adhesive interfaces.

Recently cell-cell interaction studies and high resolution structural studies have converged on a model that proposes the following: 1. Calcium binding induces conformational change in Domain 1 leading to detachment of the A-strand. This is a conformational transition from a “Closed” to an “Open” state. 2. The “Open” state forms a strand-crossover that is the adhesive dimer interface. A schematic diagram of the linkage between calcium binding, conformational change and dimerization is shown in Figure 2. Detailed calcium-binding studies from our lab elaborate this model to propose that binding of Ca3 generates the conformational change. This field has now matured to the point where biophysical techniques can be used to test the role of specific amino acids in the equilibria that culminate with formation of the adhesive dimer. The overall goal of our research is to understand the molecular mechanism that leads to adhesion in classical cadherins through studies of the linked equilibria in Figure 2. We use thermodynamic approaches to monitor the stability, calcium binding and assembly of the extracellular domains of cadherins.

Current Research Projects test the following hypotheses:

1. Ca3 is the primary player in the physical linkage between Domains 1 and 2 and in the conformational transition from the “Closed” to the “Open” state.
2. The “Opening” of the A-strand requires the undocking of W2 from the hydrophobic pocket.
3. The adhesive structure is a strand crossover structure.
4. Calcium binding modifies the kinetics of assembly and disassembly of the strand crossover species.

Honors Theses:

Magee III, Louis Coke (2022) Increasing The Student Activity Fee (full text)

Boydstun, Anna Grace (2022) Solubilizing M13-containing Protein in Low Levels of Choline Glycolate

Dulaney, Sawyer McCullough (2022) Covalent Modification of Recombinant Protein with Reactive Thiols

Taylor, Bailey Christian (2022) Covalent Modification of Recombinant Protein with Reactive Thiols

King, Ashley (2021) Bringing Biochemistry Home: Transforming Milk into Yogurt (full text)

Smith, Emilie (2021) Covalent Modification Of Genetically Engineered Polymers With BODIPY Fluorophores (full text)

Velazquez, Alexander (2021) Coronary Artery Disease: An Analysis of its Biochemical, Physiological, and Sociological Causes and Effects (full text)

Pahlevan, Nader (2021) Has Maize Overtaken Our Reality? A Personal Briefing, Biochemical Comparison, Agrigenomics, and History of Maize (full text)

Bracken, Amy K. (2020) Isolation, Identification, and Investigation of a Novel Bioactive Furanocoumarin from Leaves of Amyris elemifera (full text)

Pisciotta, Kyler (2020) Dimerization of Neural Cadherin in the Presence of Low Calcium (full text)

Berry, Hunter (2019) Time- and pH- dependent proteolysis of Engineered Proteins by Collagenase (full text)

Smith, Elaine Wallin (2019) Exploration of Thiol-Michael Addition Bioconjugation to Extend Polymers of a Protein-Based Hydrogel (full text)

Boddie, Patrick P (2018) Purification Protocol Development and Analysis of Binding Properties of Calmodulin Collagen-Like Protein (full text)

Carroll, Austin (2018) Assembly of a Protein-based Hydrogel as a Vehicle for In Situ Drug Delivery (full text)

Miscevic, Masa (2018) Development of a Gel Assay for Analysis of Bovine Milk Casein (full text)

Ramsaroop, Taylor (2017) Quercitrin and Afzelin Isolation: Chemical Synthesis of a Novel Methicillin-Resistant Staphylococcus Aureus (MRSA) Antibiotic Analogue. (full text)

Ritter, Dylan (2017) Cadmium Disruption of Calcium-Dependent Dimerization of Neural Cadherin. (full text)

Vaughan, Peyton (2017) Cytotoxicity Assay of Self-Assembling Protein-Based Biomaterials. (full text)

Barnett, Jessica Elizabeth (2017) Hinge Sequence Elements in Epithelial Cadherin Form and Function. (full text)

Calcote, Victoria (2016) Method Development Toward the Analysis of the Functionalization of Proteins. (full text)

Caron, Emilie R. (2016) Paleolithic Protection in a Western World: A Look Into Preagricultural Nutrition as a Remedy for the Diseases of Civilization. (full text)

Hitt, Mary Moses (2016) The Evolution of the Sugarcoated American Food Market and the Paradox of Artificial Sweeteners. (full text)

Abadie, Catherine (2015) A Study of the Impact of pH on the Structure and Stability of Epithelial Cadherin. (full text)

Cegielski, Alison R. (2015) Breastfeeding: Physiological and Cultural Influences. (full text)

Coghlan, Martha Kaitlyn (2015) X-Dimer Mutations and their Effects on the Folding Stability and Assembly of ECAD12 at the K14-D138 Interface. (full text)

Edmondson, Molly (2015) Characterization of Epithelial Cadherin Domain 1. (full text)

McClearn, Victoria (2015) The Dimerization Kinetics of NCAD12 with a Mutated Cis-X-Pro Bond. (full text)

Straughan, Ross E. (2015) A Computational Comparison of the Hydrophobic Pocket of Neural and Epithelial Cadherins for the Purpose of Identifying a Selective Inhibitor. (full text)

Treadway, Brent (2015) Effects of Synthetic Blood Plasma on Calcium Dependent Dimerization of NCAD12. (full text)

Humphries, Charles Ryan (2014) Domain-Specific Probes for Calcium Binding to Neural Cadherin. (full text)

Lee, David (2014) The Origins of an Everyday Behavior: Why do People Share Meals? (full text)

Villarreal, Eric (2014) Energy Drinks And Caffeine: The Science Behind The Billion- Dollar Industry. (full text)

Phongam, Natalie Rene (2013) "Development of a Quantitative Bead Aggregation Assay for Determining Assembly of Adhesive Dimers in Neural-Cadherins"

Walters, Candice Ashton (2013) "Ph Dependent Proteolysis Of Neural Cadherin" (full text)

Dove, Matthew Lafayette (2012) "The Effect of Calcium Concentration and pH Levels on the Proteolysis of the Two-Domain Neural-Cadherin Construct" (full text)

Fair, Logan Dwayne (2012) "The Role of Cortisol in Modern Society: Linking Psychosocial Stress and Health" (full text)

Jackson, Jonathon Troy (2012) 'Your Body is a Temple:' Type-2 Diabetes in Mississippi and the Potential Role of the Black Church in Diabetes Education and Intervention" (full text)

Rodgers, Ariel Jeanette (2012) "The Effects of the Histidine-Alanine-Valine Peptide on the Dimerization of Neural Cadherin" (full text)

Abdeen, Corey Ryan (2010) "Investigation of the Global Stability of Neural Cadherin's Amino-terminal Extracellular Domain (NCAD-1)"

Clark, Elaine Ann (2009) "Neural Cadherin: A Study of Domain 1."

Rogers, Brittany Nicole (2009) "Dissection of NCAD12: Distinctive Characteristics of Domains 1 and 2" (full text)

Udemgba, Chinelo (2009) "Testing A Model: Ca2+ Induced Exposure of Tryptophan in Neural-Cadherins" (full text)

Wood, Thomas Thayer (2009) "Calcium Binding Affinity Properties of Neural Cadherin Domains 1 and 2" (full text)

Huang, Derek Chen (2007) "The Protective Effects of Fructose-1,6-Biphosphate on MRC-5 Lung Fibroblast Cells Under Ischemic Conditions"

Patrick, Charles Andrew (2007) “The Computational Characterization of Surface Charges in Domain 2 Constructs of Neural and Epithelial Cadherin

Mccool, John Kyle (2007) "Stability Studies of Domain 2 of Neural Cadherin"

Anazia, Gregg Oyemachi (2005) "Size Exclusion Chromatography: Estimation of Protein Shape"

Oyetunji, Shakirat Omolara (2005) "Spectroscopic Studies of Site 3 Mutants of Calmodulin"

Rutherford, John Matthew (2005) "Sedimentation Analysis of Interactions between Extracellular Domains of Epithelial Cadherin"

Housley, Nicole Ann Gray (2004) "Characterization and Stability Studies of Epithelial Cadherin Domain 2"

Harkins, James Patrick (2002) "Characterization of Quadruplex DNA in Varying Salt Concentrations"

Kirk, Meredith Leigh (2001) "The Binding Behavior of Calcium to Calmodulin"