title: Assembling viral channel forming proteins: Vpu from HIV-1.
abstract: Different routes of assembly are probed for the transmembrane domain (TMD) of the bitopic membrane protein Vpu from HIV-1. Vpu is responsible for the amplification of viral release from the host cell. The mode of action includes (i) heteroassembly with host factors and (ii) the formation of homo-oligomers, which are able to conduct ions across the lipid membrane. Two different routes of assembling short sequences of the N terminus, including the TMD of Vpu, Vpu1-32, and Vpu8-26, are presented by using a combination of classical molecular dynamics (MD) simulations combined with a docking approach. The rim of alanines (Ala-8, -11, -15, and -19) resembles an interlocking motif for the sequential assembly into a dimer and trimer. Simultaneous assembly results in oligomeric bundles (trimers to pentamers) with either tryptophans (Trp-23) or purely hydrophobic residues facing the center. Bundles, with serines facing the pore (Ser-24), are energetically not the lowest structures. For pentameric bundles with Ser-24 facing the pore, no water column develops during a short 25 ns MD simulation.
authors.affiliation: Institute of Biophotonics, School of Biomedical Science and Engineering and Biophotonics and Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Li
authors.forename: Hao-Jen
authors.initials: HJ
authors.lastname: Hsu
authors.forename: Wolfgang B
authors.initials: WB
authors.lastname: Fischer
mesh_terms: D015497:HIV-1 / Q000378:metabolism; D054298:Human Immunodeficiency Virus Proteins; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins