Construction of a binding site for human immunodeficiency virus type 1 gp120 in rat CD4
Schockmel GA, Somoza C, Davis SJ, Williams AF, Healey D. (1992), J Exp Med. 175, 301-4
The human immunodeficiency virus (HIV-1) infects T lymphocytes via an interaction between the virus envelope glycoprotein gp120 and the CD4 antigen of T helper cells. Previous studies demonstrated that mutations in various regions of CD4 domain 1 lead to the loss of gp120 binding. In the present study the gp120 binding site was constructed in rat CD4 by replacing rat with human CD4 sequence. A series of mutants was constructed the best of which bound gp120 with an affinity only twofold less than that of human CD4. The data indicate that the gp120 binding site of human CD4 is constituted by residues 33-58 of domain 1.
(A) Models for human and rat CD4. N-linked glycosylation sites are represented by ball and sticks. (B) The structure of CD4 domain 1 as in references 11 and 12. The filled region shows the segment of mutant 6 that is identical to human CD4. (C) Human and rat CD4 sequences (3, 4) in domains 1 and 2 that were exchanged in the mutants are underlined, with β strands assigned as in references 11 and 12. The dots under the rat sequence mark identical residues in the two species.