Short Communication: Fine Definition of a Conserved CCR5-Binding Region on the Human Immunodeficiency Virus Type 1 Glycoprotein 120

A previous study implicated a conserved surface of the human immunodeficiency virus (HIV-1) gp120 exterior envelope glycoprotein in binding the CCR5 viral coreceptor (Rizzuto C, Wyatt R, Hernández-Ramos N, Sun Y, Kwong PD, Hendrickson WA, and Sodroski J: Science 1998;280:1949–1953). Additional mutagenesis indicates that important residues in this region for CCR5 binding are Ile-420, Lys-421, Gln-422, Pro-438, and Gly-441. These highly conserved residues are located on two strands that connect the gp120 bridging sheet and outer domain, suggesting a mechanism whereby interdomain conformational shifts induced by CD4 binding could facilitate CCR5 binding.