Rapid H NMR Transverse Relaxation of Perdeuterated Lipid Acyl Chains of Membrane with Bound Viral Fusion Peptide Supports Large-Amplitude Motions of These Chains That Can Catalyze Membrane Fusion

An early step in cellular infection by a membrane-enveloped virus like HIV or influenza is joining (fusion) of the viral and cell membranes. Fusion is catalyzed by a viral protein that typically includes an apolar "fusion peptide" (fp) segment that binds the target membrane prior to fusion. In this study, the effects of nonhomologous HIV and influenza fp's on lipid acyl chain motion are probed with H NMR transverse relaxation rates ('s) of a perdeuterated DMPC membrane. Measurements were made between 35 and 0 °C, which brackets the membrane liquid-crystalline-to-gel phase transitions. Samples were made with either HIV "GPfp" at pH 7 or influenza "HAfp" at pH 5 or 7. GPfp induces vesicle fusion at pH 7, and HAfp induces more fusion at pH 5 vs 7. GPfp bound to DMPC adopts an intermolecular antiparallel β sheet structure, whereas HAfp is a monomer helical hairpin. The 's of the no peptide and HAfp, pH 7, samples increase gradually as temperature is lowered. The 's of GPfp and HAfp, pH 5, samples have very different temperature dependence, with a ∼10× increase in when temperature is reduced from 25 to 20 °C and smaller but still substantial 's at 10 and 0 °C. The large 's with GPfp and HAfp, pH 5, are consistent with large-amplitude motions of lipid acyl chains that can aid fusion catalysis by increasing the population of chains near the aqueous phase, which is the chain location for transition states between membrane fusion intermediates.