Preferential association of apocytochrome c with negatively charged phospholipids in mixed model membranes

The mitochondrial precursor protein, apocytochrome c, binds to model membranes containing negatively charged phospholipids (Rietveld, A., Sijens, R., Verkleij, A.J. and Kruijff, B. (1983) EMBO J. 2, 907-913). In the present paper the effect of apocytochrome c on the lipid distribution in model membranes, consisting of neutral and acidic phospholipids, is examined. Both ESR and fluorescence energy transfer experiments show that the protein preferentially interacts with the negatively charged phospholipid in the mixed model membranes. Semi-quantitative analysis of the fluorescence energy transfer from the single tryptophan in apocytochrome c to the parinaric acid in phosphatidylserine or phosphatidylcholine in mixed bovine brain phosphatidylserine/egg phosphatidylcholine vesicles reveals and average donor-acceptor distance of 22-26 A and 26-30 A for phosphatidylserine and phosphatidylcholine, respectively. In addition, these experiments demonstrate that this preferential interaction does not induce the separation of large domains enriched in complexes of apocytochrome c with negatively charged phospholipids and domains enriched in neutral lipids.     

HIV vaccine: it may take two to tango, but no party time yet

In a recent summary of integrase sequences, primary integrase inhibitor mutations were rare. In a review of integrase inhibitor-naïve Australian HIV-1 sequences, primary mutations were not identified, although the accessory mutation G140S was detected. A link with previous antiretroviral therapy, intra-subtype B divergence across the integrase gene and transmission of integrase polymorphisms were also noted. Based on these findings, we would recommend ongoing surveillance of integrase mutations, and integrase region sequencing for patients prior to commencement of integrase inhibitors.