Oral Presentation 2014 International Biophysics Congress

Modulation of the Mechanosensitive channel of small conductance by cardiolipin (#68)

Pietro Ridone 1 , Rong Chen 2 , Samantha Maguire 3 , Boris Martinac 1 4 , Andrew R. Battle 3
  1. Victor Chang Cardiac Research Institute, Darlinghurst, NWS, Australia
  2. Research School of Biology, Australian National University, Canberra, ACT, Australia
  3. School of Pharmacy and Griffith Health Institute, Griffith University, Gold Coast Campus, QLD, Australia
  4. St Vincents Clinical School, The University of New South Wales, Kensington, NSW, Australia

The Mechanosensitive channel of Small conductance (MscS) of E. coli. senses membrane  tension and opens to prevent hypoosmotic shock to the bacterium [1]. Cardiolipin is present in the inner membrane of E. coli and induction of cardiolipin biosynthesis has been linked to osmotic stress response in E. coli [2]. Previous studies showed that this channel co-localizes with cardiolipin at the poles of the bacterium [3], and that cardiolipin interaction with MscS causes  increase in closing frequency  of the channel when the channel is reconstituted into proteoliposomes[4]. However the physiological relevance of this phenomenon remains unclear. Furthermore, cholesterol has been shown to influence MscS properties [5]. Preliminary molecular modelling studies have shown a strong interaction of residues R46 and L60 with cardiolipin. Electrophysiological results from mutagenesis studies in which  these residues were replaced by alanine  suggest that these positively charged side chains  play an important role in channel gating by interacting with negatively charged cardiolipin  which  is reported in our study.

  1. Martinac B, Curr Top Membr. 2007 58, 25
  2. Romantsov T, Helbig S, Culham DE, Gill C, Stalker L and Wood JM, Molecular Microbiology 2007 64(6), 1455–1465.
  3. Romantsov T, Battle AR, Hendel JL, Martinac B and Wood JM, Journal of Bacteriology 2010, 192 (4),. 912–924
  4. Battle AR, Nomura T, Martinac B, Biophys J 2011, 100 S1, 278
  5. Nomura T, Cranfield CG, Deplazes E, Owen DM, Macmillian A, Battle AR, Constantine M, Sokabe M, Martinac B. Proc Natl. Acad Sci USA 2012, 109, 8770