ИСТИНА

Mutations of filamin C (FLNC) often correlate with the certain types of cardiomyopathies. However, molecular mechanisms underlying this pathology remain poorly investigated. FLNC have a complex quaternary structure, participates in organization and anchoring of actin cytoskeleton to a cell membrane. It is supposed that proper structure of FLNC is dependent on molecular chaperons and among them on small heat shock proteins (sHsp). Therefore, we were interested in the interaction of FLNC with different sHsp. Utilizing molecular cloning and biochemical methods, we obtained untagged recombinant C-terminal fragment of FLNC containing 22-24th Ig-like domains and a mutated form of this fragment carrying p.Glu2472_Asn2473delAsp mutation associated with restrictive cardiomyopathy. The mutation affects stability of FLNC fragment decreasing the temperature of thermal transition thus demonstrating significant structural changes. Chemical crosslinking with glutaraldehyde and size exclusion chromatography revealed specific interaction of the wild type FLNC fragment with HspB7, but not with other sHsp. The data of native gel electrophoresis indicate that the wild type FLNC fragment and its mutated form interact with HspB7 in a different way. The results presented indicate that HspB7 can be involved in the interaction and regulation of FLNC and mutation of FLNC can affect this interaction. This investigation was supported by RSF (grant № 22-74-00013).