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Vpu is an 81 amino acid integral membrane protein encoded by HIV-1. Its alpha-helical transmembrane (TM) domain (residues approximately 6-28) enhances virion release by oligomerizing into bundles and forming ion-conducting channels across the plasma membrane. Its cytoplasmic domain (residues approximately 29-81) is also alpha-helical and binds to the transmembrane protein CD4, inducing its degradation. Mutations within the TM domain have been found to abrogate enhanced particle release from the infected cell (Tiganos et al. Virology (1998) 251 96-107). A series of computational models of monomeric, pentameric and hexameric Vpu(1-31) mutants have been constructed, embedded in fully hydrated lipid bilayers and subjected to a 3 ns molecular dynamics (MD) simulation. None of the mutations has any destabilizing effect on the secondary and tertiary structure. One of the mutants, in which the position of a tryptophan residue within the TM domain is altered, is known not to induce CD4 degradation; an extended kinked model of this mutant has been generated (Vpu(1-52)IVW-k) and during subsequent MD simulations, the bend between the TM and a part of the cytoplasmic domain is found to unwind and a complex salt bridge involving Lys-37 is formed.

Original publication

DOI

10.1016/j.bbamem.2005.07.012

Type

Journal article

Journal

Biochim Biophys Acta

Publication Date

01/10/2005

Volume

1716

Pages

1 - 10

Keywords

Amino Acid Sequence, CD4 Antigens, Cell Membrane, Cytoplasm, DNA Mutational Analysis, HIV-1, Human Immunodeficiency Virus Proteins, Ions, Lipid Bilayers, Lysine, Models, Molecular, Molecular Sequence Data, Mutation, Protein Conformation, Protein Structure, Secondary, Protein Structure, Tertiary, Software, Time Factors, Tryptophan, Viral Regulatory and Accessory Proteins, Water