Direct in vitro binding of full-length human immunodeficiency virus type 1 Nef protein to CD4 cytoplasmic domain.
The Nef protein of the simian and human immunodeficiency viruses is known to directly bind and downregulate the CD4 receptor. Although the molecular mechanism is well understood, direct binding of Nef and CD4 is difficult to demonstrate and is believed to be of low affinity. Applying nuclear magnetic resonance and fluorescence spectroscopy, we biophysically reevaluated the CD4-Nef complex and found the dissociation constant to be in the submicromolar range. We conclude that additional, so far disregarded residues in the N terminus of Nef are important for interaction with CD4.
Preusser
A
A
Institut für Molekulare Biotechnologie, D-07745 Jena, Germany.
Briese
L
L
Baur
A S
AS
Willbold
D
D
D000595:Amino Acid Sequence; D015704:CD4 Antigens / Q000737:chemistry* / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D015536:Down-Regulation; D015693:Gene Products, nef / Q000737:chemistry* / Q000378:metabolism*; D015497:HIV-1; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013816:Thermodynamics; D054311:nef Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus