Seminarium Zakładu Biofizyki

ATPases Associated with various Activities (AAA+) are a family of proteins that perform multiple cellular functions involving mechanical work, such as disassembly of macromolecular complexes, unwinding of DNA double helix, protein transport along microtubules etc. The common structural feature of AAA+ ATPases is the formation of hexameric rings with the central pore, in which substrate processing takes place. Our laboratory has been investigating several members of the AAA+ family, including bacterial ClpB and its distant mammalian homologue SKD3. ClpB resolubilizes aggregated proteins under cellular stress conditions and is essential for infectivity and proliferation of multiple pathogenic microorganisms. We are currently identifying small-molecule inhibitors of ClpB which might become leads for novel antimicrobials. SKD3 is a mitochondrial protein that has been linked to multiple human pathologies, including neutropenia, but its biological function is currently unknown. To begin resolving the structure/function relationship in SKD3, we characterized its self-association properties and discovered that, unlike most AAA+ proteins, SKD3 assembles into dodecamers. A physiological significance of the non-canonical structure of SKD3 remains to be determined.