The Homotrimeric HIV-1 Viral Coat Protein GP41 is Highly Dynamic

Abstract

A solution NMR study on the structure and dynamics of the homotrimeric gp41 complex, reconstituted in dodecyl phosphatidylcholine (DPC) micelles, is presented. Observed resonances were assigned to the fusion peptide (FP), N-terminal heptad repeat (NHR) and immuno-dominant loop region (IL), whereas the C-terminal heptad repeat (CHR) region, membrane proximal external region (MPER) and transmembrane helix (TM) remain completely invisible to solution NMR. 15N relaxation data reveal a high degree of intrinsic mobility: The a-helical fusion peptide (FP) exhibits high amplitude motion on the fast nanosecond time scale relative to the NHR region. The linker between NHR and CHR shows both fast and slow (microsecond) motions.Figure 1: Homotrimeric gp41 shows a high degree of intrinsic mobility. Our data are compatible with the protein switching on a microsecond time scale between the pre-hairpin intermediate, three-helical bundle state, and the late-fusion, anti-parallel six-helical bundle. MPER and TM are not shown since their conformation cannot be evaluated from the available solution NMR data. While MPER and TM are absent from the spectra, the FP shows the most intense resonances, which excludes a strong interaction between FP and TM region.View Large Image | View Hi-Res Image | Download PowerPoint Slide