| Summary: | 博士 === 國立陽明大學 === 生醫光電研究所 === 103 === Vpu is a 9-kilodalton type I membrane protein in the genome of HIV-1 with a
length of 81 amino acids. Vpu is unique to HIV-1 and not found in HIV-2. Vpu is
responsible for the amplification of viral release from the host cell. Two domains of
Vpu are related to two biological activities: (i) the C-terminal hydrophilic cytoplasmic
domain is associated with the induction of CD4 degradation in the endoplasmic
reticulum; (ii) the N-terminal hydrophobic transmembrane domain (TMD) is
associated with the release of the virus from HIV-1 infected cells.
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The assumption is that viral channel forming proteins are produced and expressed
in the endoplasmic reticulum as a single units and exist as monomers until they
assemble into oligomers. First part, Alanine rim (Ala8/11/15/19) resembles an
interlocking motif for the sequential assembly into a dimer. Vpu is assembled into
oligomeric bundles (Trimers, Tetramers and 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. Second part, a
bundle-like structure of Vpu is proposed by assembling Vpu into a homo-pentameric
bundle around prepositioned Na+, K+, Ca2+ or Cl- ions. For bundles with the lowest
energy, the TMDs generate a hydrophobic pore. Third part, the focus is on the
interaction of the TMDs of Vpu with host factors such as BST-2, NTB-A and CD4.
Binding poses and adopted tilt angles of the dimers are analyzed and correlated with
experimentally derived activity data from literature.
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