The activator domain of bacterial collagenases drives collagen recognition, unwinding and processing
Serwanja, J.; Wieland, A. C.; Haubenhofer, A.; Brandstetter, H.; Schönauer, E.
Show abstract
Collagens form the resilient backbone of the extracellular matrix in mammals. Only few proteases are able to digest triple-helical collagen. Clostridial collagenases can efficiently process collagen. However, little is known about the mechanism of bacterial collagenolysis of either soluble collagen or the multi-hierarchically assembled, insoluble collagen fibers. Here we present a functional analysis of the distinct roles of the individual domains of collagenase G (ColG) from Hathewaya histolytica. A broad array of biochemical, biophysical, and enzymatic data consistently revealed unexpected synergistic and antagonistic interactions between the activator, peptidase and collagen-binding domains. We found the non-catalytic activator domain to act as a master regulator, coordinating the complex interactions to specifically recognize and process the diverse physiological substrates. The results presented here enable multiple applications such as the engineering of collagenase variants with selectivity for defined substrate states.
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