Influence of M680I and M694V mutations on pyrin's domain B30.2 tertiary structure and it's complex formation ability with caspase-1

Abstract

The M680I and M694V mutations located in the B30.2 pyrin domain are responsible for the manifestation of the most common forms of Familial Mediterranean fever. It is well known that a malfunction of the pyrin-caspase-1 complex is the main cause of inflammation in FMF. The purpose of this study was to identify possible changes in the tertiary structure of mutated B30.2 domain and to determine their potential consequences in the formation of the pyrin-caspase-1 complex. Using computer modeling, it was found that the above mutations change the tertiary structure of B30.2 domain, causing shifts of binding sites and altering the energy of interaction between B30.2 and caspase-1.