Unsaturated Lipid Accelerates Formation of Oligomeric β‑Sheet Structure of GP41 Fusion Peptide in Model Cell Membrane

Membrane fusion of
the viral and host cell membranes is the initial
step of virus infection and is catalyzed by fusion peptides. Although
the β-sheet structure of fusion peptides has been proposed to be the most important fusion-active
conformation, it is still very challenging to experimentally identify
different types of β-sheet structures at the cell membrane surface
in situ and in real time. In this work, we demonstrate that the interface-sensitive
amide II spectral signals of protein backbones, generated by the sum
frequency generation vibrational spectroscopy, provide a sensitive
probe for directly capturing the formation of oligomeric β-sheet
structure of fusion peptides. Using human immunodeficiency virus (HIV)
glycoprotein GP41 fusing peptide (FP23) as the model, we find that
formation speed of oligomeric β-sheet structure depends on lipid
unsaturation. The unsaturated lipid such as POPG can accelerate formation
of oligomeric β-sheet structure of FP23. The β-sheet structure
is more deeply inserted into the hydrophobic region of the POPG bilayer
than the α-helical segment. This work will pave the way for
future researches on capturing intermediate structures during membrane
fusion processes and revealing the fusion mechanism.