Cathepsin K and Collagen Degradation


 Jadwiga Kaleta, Nelson Chen, Dr. Jana Selent

 


Background 

Cathepsin K is the predominant osteoclast protease that degrades type I collagen. The collagenase activity of cathepsin K depends on the complex formation with chondroitin sulphate A (CSA). Prevention of the complex formation between cathepsin K and CSA (cathepsin K/CSA) by a selective inhibitor may present a novel therapeutic approach to decrease abnormal bone degradation such as in osteoporosis.

Goal 

The aim of the project is the structural characterization of the collagenolytically active cathepsin K/CSA complex as a prerequisite for the development of selective inhibitors.

 
 

 

Fluroescence Polarization (FP)

 

The binding of CSA* (CSA*: fluorescein labelled CSA) to cathepsin K can be monitored through the rotation speed of the complex which depends on the molecular size (A: fast rotation of free CS A; B: slow  rotation of cathepsin K/CS A complex).

  

Atomic Force Microscopy (AFM)

  

 

 

The shape of the collagenolytically active cathepsin K/CSA complex and also the interaction with collagen type I are studied through AFM. The AFM image of a 1/1 molar ratio of cathepsin K and CSA suggests the formation of chain-like complexes (arrows).