Biophysical characterization of the plakin family

Al-Jassar, Caezar (2013). Biophysical characterization of the plakin family. University of Birmingham. Ph.D.

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Abstract

The desmosome is an inter-cellular complex required for strong cell-cell adhesion in skin and heart tissue. The plakin family of proteins is important to the desmosome as their main function is to act as linkers between the cell surface and cytoskeleton. The structures, dynamics, impact of heart disease causing mutations and interactions of these component domains have remained largely unknown. In order to better understand this, biophysical techniques were used to shed light into the specific effects of pathological mutations using complementary techniques including nuclear magnetic resonance spectroscopy, small angle X-ray scattering and X-ray crystallography.

Novel insights included the modular organization and flexibility of serial spectrin repeat constructs in the N-terminal plakin domain was established. Biophysical characterization of a variety of plakin family C-terminal tail constructs was successfully conducted in addition to understanding the molecular consequences of disease causing point mutations linked to Arryhthmogenic Right Ventricular Cardiomyopathy.

Together this provides a better understanding of the specific roles of the plakin family’s N- and C- termini in linking the desmosomal machinery on the cell membrane to the intermediate filaments.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):