Cellular respiration provides energy for life’s chemical reactions, and at the heart of this process are the respiratory chain complexes. Together they can form even larger, dynamic, supercomplexes, the functional value of which is still not very well understood. In many species of the phylum Actinobacteria, one such respiratory supercomplex is permanently assembled, with a different architecture and several new subunits and intriguing features (including, at least in some species, a superoxide dismutase).


We have determined the structure of one such supercomplex from Mycobacterium smegmatis. With a single molecular complex encompassing the entire process of electron flow from quinones to oxygen and proton translocation across the membrane, we can study this process in detail, using computational modelling and structure-function studies of mutant versions. The in vitro and in vivo function of the novel subunits and of complexes harbouring mechanistically important mutations will also be explored, as well as regulation cross-talk with other resiratory pathways. We are also working on making homology models and determining the structures of supercomplexes from related species – including some very important pathogens.
 

The project will give us a clearer picture of how respiratory supercomplexes work, and may also explain why they are permanently assembled in Actinobacteria. The structural and functional data can also be exploited for the development of new antimicrobial agents.
 

Together, our four research groups (Högbom, Brzezinski, Ädelroth and Kaila) cover a broad method base; from structural biology and molecular dynamics to in vitro/in vivo respiratory complex function. ~10 scientists are currently working with different aspects of the project. When positions are made available they will be announced here (with links to the respective job ads at the Stockholm University ”Available Jobs” website).

 

Contact details:

Professor Martin Högbom

Professor Peter Brzezinski

Professor Pia Ädelroth

Professor Ville Kaila

Dan Sjöstrand (staff researcher, project coordinator)

 

References:

Wiseman B et al. Structure of a functional obligate complex III2IV2 respiratory supercomplex from Mycobacterium smegmatis. Nat Struct Mol Biol. 2018 Dec;25(12):1128-1136.