Restriction of lipid motion in membranes triggered by β-sheet aggregation of the anti-apoptotic BH4 domain
2008 (English)In: The FEBS Journal, ISSN 1742-464X, Vol. 275, no 3, 561-572 p.Article in journal (Refereed) Published
The regulative BH4 domain of human Bcl-2 protein exerts its anti-apoptic activity via the mitochondrion. In the present study, we investigated the molecular interactions of this domain with negatively charged liposomes mimicking the outer mitochondrial membrane. To model the overproduction of Bcl-2 found in cancer processes, we studied the impact of elevated concentrations of its regulative BH4 segment on these mitochondrial membranes from the peptide and lipid perspective. Combined solid state 2H-NMR and differential scanning calorimetry revealed the coexistence of small sized fluid and rigid membrane domains over a large temperature range, which is confirmed by 31P-NMR at 30 °C. The latter are stabilized, in a cholesterol-like manner, by the presence of a BH4 peptide. In the same time scale, the reduction of the headgroup order is seen in the static 14N and 31P-NMR spectra when BH4 inserts into the bilayers. Indeed, attenuated total reflection spectroscopy indicated a dominant aggregated β-sheet secondary structure of BH4 with a 42° tilt relative to the membrane surface. These results are discussed in terms of membrane stabilization versus apoptotic mechanisms at the outer mitochondrial membrane location.
Place, publisher, year, edition, pages
2008. Vol. 275, no 3, 561-572 p.
apoptosis, BH4 domain, membrane, protein-lipid interactions, solid state NMR
IdentifiersURN: urn:nbn:se:umu:diva-7994DOI: doi:10.1111/j.1742-4658.2007.06222.xOAI: oai:DiVA.org:umu-7994DiVA: diva2:147665