The HIV-1 co-receptor CCR5 binds to alpha-catenin, a component of the cellular cytoskeleton.
The chemokine receptors CCR5 and CXCR4 belong to the family of seven transmembrane-spanning G protein-coupled receptors, which have diverse functions in host cell defense and are associated with numerous diseases. CCR5 and CXCR4 are known as co-receptors for entry of HIV-1. In this study the intracellular carboxy-terminus of CCR5, which is deleted in HIV-infected long-term non-progressors, was shown to interact with the carboxy-terminus of alpha-catenin, a component of the cytoskeleton, in a yeast two-hybrid screen. This interaction was verified in mammalian cells. Furthermore, the interaction of alpha-catenin with CCR5 and CXCR4 at endogenous protein levels was demonstrated in PM1 T-lymphocytes, a host cell line of HIV-1. Our results suggest that alpha-catenin links CCR5 and CXCR4 to the cytoskeleton and is involved in the organization of these receptors at the membrane, thereby possibly affecting HIV-1 infection.
Schweneker
Marc
M
Institute of Medical Virology, University of Zurich, 8028 Zurich, Switzerland; Institute of Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
Bachmann
André S
AS
Moelling
Karin
K
D019943:Amino Acid Substitution; D001665:Binding Sites; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000196:embryology / Q000378:metabolism*; D011485:Protein Binding; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D015728:Receptors, HIV / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D051178:alpha Catenin
C495273:CTNNA1 protein, human; D003598:Cytoskeletal Proteins; D019713:Receptors, CCR5; D015728:Receptors, HIV; D011994:Recombinant Proteins; D051178:alpha Catenin