Normal-mode analysis suggests important flexibility between the two N-terminal domains of CD4 and supports the hypothesis of a conformational change in CD4 upon HIV binding.
Human CD4 is the receptor for human immunodeficiency virus (HIV). It is well established that the first domain of CD4 binds with high affinity to gp120, an envelope protein of HIV, but it has also been demonstrated that amino acids located in its second domain, within or close to residues 120-127 or 163-166 (lying 15 A away from the binding site), play a role in virus infectivity. We show here that these two stretches of amino acids happen to be important for the largest amplitude motion obtained with the normal-mode theory for the two N-terminal domains of human CD4: an overall rigid-body displacement of one domain with respect to the other. Such a 'hinge-bending' motion is unexpected since these two domains were found by crystallographers to be tightly abutting. On the other hand, since for several proteins the hinge-bending motion experimentally observed upon ligand binding was found to be similar to the largest amplitude motion obtained with the normal-mode theory for these proteins, our results suggest that CD4 may undergo such a kind of conformational change upon HIV binding.
Sanejouand
Y H
YH
Laboratoire de Physique Quantique, UMR, CNRS, IRSAMC, Université Paul-Sabatier, Toulouse, France.
D015704:CD4 Antigens / Q000737:chemistry*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D015704:CD4 Antigens