Protein ensembles link genotype to phenotype
Fig 5
Phenotype switch of HIV-1 entry.
Schematic diagram representing the initial process of the HIV-1 entry that led to fusion between the viral and the host cell membranes. The gp120 trimer undergoes a conformational change upon binding to cellular receptor CD4, exposing the variable loop V3. The V3 loop binds to the coreceptor (CCR5 and CXCR4), triggering the entry process. The wild-type V3 loop with positively and negatively charged residues at positions 304 and 322, respectively, recognizes CCR5. A phonotype switch by a mutation from a negatively to a positively charged residue at position 322 in the V3 loop alters coreceptor recognition to CXCR4. Modeled structures are the crystal structures of gp120 (PDB code: 24BC), CCR5 (PDB code: 4MBS), and CXCR4 (PDB code: 3ODU) and the NMR structure of V3 loop (PDB code: 2ESX). CCR5, C-C chemokine receptor type 5; CXCR4, C-X-C chemokine receptor type 4; PDB, Protein Data Bank.