Abstract
The modular protein Alix is a central node in endosomal-lysosomal trafficking and the budding of human immunodeficiency virus (HIV)-1. The Gag p6 protein of HIV-1 contains a LYPx(n)LxxL motif that is required for Alix-mediated budding and binds a region of Alix spanning residues 360-702. The structure of this fragment of Alix has the shape of the letter 'V' and is termed the V domain. The V domain has a topologically complex arrangement of 11 alpha-helices, with connecting loops that cross three times between the two arms of the V. The conserved residue Phe676 is at the center of a large hydrophobic pocket and is crucial for binding to a peptide model of HIV-1 p6. Overexpression of the V domain inhibits HIV-1 release from cells. This inhibition of release is reversed by mutations that block binding of the Alix V domain to p6.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Binding Sites
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Calcium-Binding Proteins / chemistry*
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Calcium-Binding Proteins / metabolism*
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Carrier Proteins / chemistry*
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Carrier Proteins / metabolism*
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Cell Cycle Proteins / chemistry*
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Cell Cycle Proteins / metabolism*
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Crystallography, X-Ray
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Endosomal Sorting Complexes Required for Transport
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Gene Products, gag / metabolism
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HIV-1 / physiology*
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HIV-1 / ultrastructure
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HeLa Cells
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Humans
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Hydrophobic and Hydrophilic Interactions
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Models, Molecular
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Molecular Sequence Data
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Phenylalanine
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Protein Binding
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Protein Structure, Tertiary
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Structure-Activity Relationship
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gag Gene Products, Human Immunodeficiency Virus
Substances
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Calcium-Binding Proteins
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Carrier Proteins
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Cell Cycle Proteins
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Endosomal Sorting Complexes Required for Transport
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Gene Products, gag
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PDCD6IP protein, human
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gag Gene Products, Human Immunodeficiency Virus
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p6 gag protein, Human immunodeficiency virus 1
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Phenylalanine