Studies of HIV gp160 Envelope Protein Structure: Molecular Modeling of gp41 C-terminus

Abstract

The membrane proximal region, membrane spanning domain and C-terminus region of HIV gp41 are highly conserved and essential mechanisms for cell membrane fusion and entry. Multiple resolved structures exist for the membrane distal gp120, however little is known about the structure of membrane proximal gp41. In this study we expose the complete lack of knowledge and contradictory findings regarding the cytoplasmic C-terminus region of gp41. Our research was unable to create a working model for the C-terminus tail, although we provide a molecular model (Phyre480_553) for the gp41 ectodomain which has until now yet to be structured. The gp120-gp41 bridging region (480-553) contains 8 highly conserved sequences which could be tested for specific protective antibody binding. Our research elucidates the potential benefit of protein homology prediction and reveals the importance of both the ectodomain and membrane associating regions of gp41 as potential antigenic immune targets for future studies. Protective antibody binding spots on exposed cytoplasmic bits have yet to be accepted as a target region of interest for vaccines. Our research provides a solid methodology to synthesize a novel working model for the gp41 membrane spanning domain