Protein Science
 

The goal of the protein science team of the AoE is to understand the mechanism of skeletal disease at the molecular level. We approach this challenge using structural and functional approaches to protein biochemistry, as well as by using many of the latest techniques in proteomics to further elucidate the biochemical pathways behind cartilage and bone formation.

Principal Investigators of the Protein Science Team of the AoE

Professor Kathryn Cheah, Chair Professor, Department of Biochemistry, HKU

Professor Mingjie Zhang, Professor, Department of Biochemistry, HKUST

Dr. Danny Chan, Assistant Professor, Department of Biochemistry, HKU

Dr. Julian Tanner, Research Assistant Professor, Department of Biochemistry, HKU

Dr. Ivan Chu, Assistant Professor, Department of Chemistry, HKU

We currently work on three main projects, but also work in a number of minor projects directly related to the other sub-themes of the AoE.

Understanding the Function of Sedlin and the TRAPP complex

Sedlin is a component of a protein complex (the TRAPP complex) that transports vesicles between the ER and the golgi. Mutations in the SEDL that codes for sedlin result in the congenital disease spondyloepiphyseal dysplasia tarda (SEDT), an X-linked late-onset skeletal disorder. We are taking both a structural and functional approach to elucidating the many roles of sedlin and to understanding why mutations result in this disease.

 
 

This is the structure of sedlin, why do mutations in this protein result specifically in skeletal disease?

 

The Structural Basis of Mutant Collagen X Protein Folding/Misfolding

Collagen X is the most abundant extracellular matrix component and is synthesized specifically by hypertrophic chondrocytes. Mutations in Col10A1 result in Schmid metaphyseal chondrodysplasia (SCMD). We have recently shown in a mouse model of the disease that these mutations lead to the unfolded protein response and chondrocyte redifferentiation. We are currently probing the structural basis of mutations in collagen X and how these mutations effect correct protein folding and chain assembly.

 
 
 

The C-terminal NC-1 domain of Collagen X is rich in beta sheet structures. Mutations in this protein cause SCMD.

 
 

Chondrocyte Proteomics: Delineating Protein Networks, Communication and Signaling Pathways

Many skeletal disease result from protein misfolding, protein trafficking problems and other stresses occurring in chondrocytes. We are using Isotope Coded Affinity Tagging (ICAT) to perform comparative proteomics of chondrocytes and to elucidate the processes by which protein misfunction leads to disease.