Self-Assembly of the Viral Channel Forming Protein Vpu of Hiv-1 using Coarse-Graining Molecular Dynamics Simulations

Abstract

Vpu of human immunodeficiency virus type 1 (HIV-1) which is an 81 amino acid bitopic membrane protein known to homo-oligomerize. It is known for its ability to form channels and to assemble into host factors. The assembly process and the oligomer state of Vpu are not known. Coarse-graining molecular dynamics simulations are performed with full-length Vpu in lipid bilayers. Full-length Vpu is constructed by linking an experimentally derived structural model of the cytoplasm domain with a computationally generated transmembrane domain (TMD). Simulation boxes are generated harboring selected numbers of VPUs. The simulations identify that Vpu assembles via several binding sites into a series of oligomeric states. Most striking, in a simulation of four Vpu's the proteins form a symmetric bundle which is a close match to known channel architectures. The tetramer is followed a dimer formation. Not only TMDs but also cytoplasm domains are involved in the dynamics of self-assembly.