Fusion Peptide of Gp41 Self Associates in the Model Membrane and then Interacts with its Trans-Membrane Domain

Abstract

We have examined the peptide structure and membrane packing when the fusion peptide (FP) of gp41 was added either in the membrane alone or in the membrane containing gp41 the trans-membrane domain (TMD). Circular Dichroism (CD) measurements showed that FP is mostly in a beta sheet conformation independent of FP concentration. TMD has ∼ 30% helical, ∼25% beta sheet and the complex of TMD and FP has less alpha helix than the TMD itself, which indicates the TMD looses its alpha helical structure upon interacting with FP. DPH and TMA-DPH fluorescence anisotropy revealed that FP alone increased the interior packing of the membrane, but FP in the presence of TMD increased the interior packing at lower concentrations of FP and then decreased it at higher concentrations. FP alone increased membrane surface packing at lower concentrations but increased it at higher concentrations. In the presence of TMD, FP addition decreased surface packing cooperatively. From the lifetime of TMA-DPH in H2O and D2O we documented water penetration into the membrane. FP alone increases water penetration slightly whereas FP in presence of TMD significantly increased water penetration into the interface region of the membrane in a cooperative fashion. The fluorescence lifetime of C6NBDPC revealed that FP alone fills more space than the FP in the presence of TMD. In summary, our results clearly demonstrate that gp41 FP forms a complex with the gp41 TMD to alter both TMD structure and membrane structure. It remains to be seen whether this complex promotes membrane fusion. Supported by NIGMS grant 32707 to BRL.