Binding of the C-terminal domain of the HIV-1 capsid protein to lipid membranes: a biophysical characterization.

The capsid protein, CA, of HIV-1 forms a capsid that surrounds the viral genome. However, recent studies have shown that an important proportion of the CA molecule does not form part of this capsid, and its location and function are still unknown. In the present work we show, by using fluorescence, differential scanning calorimetry and Fourier-transform infrared spectroscopy, that the C-terminal region of CA, CA-C, is able to bind lipid vesicles in vitro in a peripheral fashion. CA-C had a greater affinity for negatively charged lipids (phosphatidic acid and phosphatidylserine) than for zwitterionic lipids [PC/Cho/SM (equimolar mixture of phosphatidylcholine, cholesterol and sphingomyelin) and phosphatidylcholine]. The interaction of CA-C with lipid membranes was supported by theoretical studies, which predicted that different regions, occurring close in the three-dimensional CA-C structure, were responsible for the binding. These results show the flexibility of CA-C to undergo conformational rearrangements in the presence of different binding partners. We hypothesize that the CA molecules that do not form part of the mature capsid might be involved in lipid-binding interactions in the inner leaflet of the virion envelope.