Premium
Assembling viral channel forming proteins: Vpu from HIV‐1
Author(s) -
Li LiHua,
Hsu HaoJen,
Fischer Wolfgang B.
Publication year - 2013
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22210
Subject(s) - trimer , chemistry , dimer , biophysics , molecular dynamics , transmembrane domain , docking (animal) , crystallography , transmembrane protein , viral protein , membrane , protein structure , stereochemistry , biochemistry , virus , virology , computational chemistry , biology , receptor , nursing , organic chemistry , medicine
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, Vpu 1–32 , and Vpu 8–26 , 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. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 517–529, 2013.