Date of Award

Spring 1993

Project Type

Dissertation

Program or Major

Biochemistry

Degree Name

Doctor of Philosophy

First Advisor

Thomas Laue

Abstract

Biglycan and decorin are small, leucine-rich proteoglycans that bind to a variety of extracellular and membrane associated molecules, regulating their biological functions. Although self-association occurs in many proteoglycans, and is thought to be important for their biological roles, little is known about the thermodynamic properties of biglycan and decorin in terms of molecular weights, stoichiometry and association constants. We have used sedimentation analysis to examine the structures and self-association of bovine articular cartilage biglycan, its core protein and GAG chains in a variety of buffers. The monomer molecular weights were 86,600 Da for intact biglycan, 44,100 Da for the core protein and 23,300 Da for the GAG chains. Under non-denaturing conditions without Zn$\sp{++}$, both biglycan and its core protein appear to form oligomers, while the GAG chains remain monomeric. Biglycan self-associates to a dimer with small amounts of higher oligomers. When 5 mM Zn$\sp{++}$ was introduced, the biglycan seems to form a predominant heptamer. The core protein appears to form extremely large and polydisperse oligomers, while the GAG chains remain predominantly monomeric.

Similar analyses have been performed on bovine skin decorin. The monomer molecular weight of skin decorin was determined as 64,700 Da. In non-denaturing solvents without Zn$\sp{++}$, decorin apparently undergoes a monomer-dimer self-association with a binding constant almost identical with that of biglycan. In buffer containing 5 mM Zn$\sp{++}$, decorin forms a heterogeneous self-associating system with the possible presence of much larger oligomer.

These observations suggest that in non-denaturing solvents with or without Zn$\sp{++}$, the core proteins of biglycan and decorin appear to play a key role in their self-association. The GAG chains are more likely to have indirect roles in modulating the self-association of core proteins.

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