title: Presence of a helix in human CD4 cytoplasmic domain promotes binding to HIV-1 Nef protein.
abstract: The Nef proteins of simian and human immunodeficiency viruses are known to directly bind and downregulate the CD4 receptor of infected cells. Recent results suggest that residues forming an alpha-helix N-cap in the CD4 cytoplasmic domain play a role in binding of CD4 to human immunodeficiency virus type 1 Nef protein. We determined the dissociation constants between Nef and several CD4 peptides that contain or do not contain the respective alpha-helix N-cap. Further, we compared helical secondary structure content of these CD4 peptide variants by circular dichroism spectroscopy. We conclude that presence of an alpha-helix in CD4 cytoplasmic domain increases CD4 affinity to Nef. In addition, the amino acid sequence of residues forming the helix N-cap influences CD4 affinity to Nef, too. Finally, the structural changes induced in Nef and CD4 upon binding to each other are investigated.
authors.affiliation: Institut für Molekulare Biotechnologie, Beutenbergstrasse 11, D-07745 Jena, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Preusser
authors.forename: Lars
authors.initials: L
authors.lastname: Briese
authors.forename: Dieter
authors.initials: D
authors.lastname: Willbold
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002942:Circular Dichroism; D015693:Gene Products, nef / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D015704:CD4 Antigens; D015693:Gene Products, nef; D010455:Peptides; D054311:nef Gene Products, Human Immunodeficiency Virus