Truncated variants of gp120 bind CD4 with high affinity and suggest a minimum CD4 binding region.

The envelope glycoprotein, gpl20, of human immuno- deficiency virus type 1 (HIV-1) binds the cellular protein CD4 with high affinity. By deletion we show that 62 N- and 20 C-terminal residues along with the Vl, V2 and V3 variable regions of gp 120 are unnecessary for CD4 binding. A 287 residue variant (ENV59), missing those 197 amino acids, binds to CD4 with high affinity. A polyclonal antibody failed to efficiently precipitate ENV59 which is consistent with the loss of immunodominant antigenic structures in the regions deleted. This suggests that ENV59 may have potential as an immunogen, able to elicit antibodies against more conserved regions of gp120. Additionally, complementing co-expressed gpl20 fragments as well as a circularly permuted molecule bind CD4, and suggest either that the molecular termini are adjacent in the folded structure, or that an N-terminal region folds into the structure unconstrained by its method of attachment to the rest of the molecule. Key words: CD4 binding/complementation/deletion mutants/gp 120/permuted variants of the molecule, do not appear to affect CD4 binding. The lack of significant CD4 binding of mutants truncated at the N-terminus, however (Dowbenko et al., 1988), suggests that the binding domain either includes N-terminal regions (Olshevsky et al., 1990; Syu et al., 1990), or that the N- terminus is required for the correct folding of the molecule. Further evidence that correctly folded gpl20 is required for CD4 binding derives from the demonstration that several monoclonal antibodies that bind only to 'conformational epitopes' in gpl2O block CD4 binding (Ho et al., 1991; Posner et al., 1991).