Fig. 2 | Nature Communications

Fig. 2

From: Selection of immunoglobulin elbow region mutations impacts interdomain conformational flexibility in HIV-1 broadly neutralizing antibodies

Fig. 2

Heavy chain FWR1 mutations in the CH103 bnAb lineage. a The mature CH103 bnAbs were isolated from an HIV-1 infected African patient24. The unmutated common ancestor (UCA) and intermediate antibodies (Is) were inferred and each mAb was produced as described previously24. The % VH mutations are indicated on the phylogram. b The location of the mutations (red) P14S (FWR1), S30G and S31G (HCDR1 proximal) that are selected in I4 are shown for the CH103 bnAb heavy chain (blue) in complex with gp120 (green). The CH103 light chain is shown in gray. The CH103-gp120 bound structure was originally solved in complex with only the outer domain of gp12024. For visualizing the location of the CH103 mutations in the context of a more fully resolved gp120, the CH103 complex structure was superimposed onto a gp120 core that included the inner domain (PDB: 4RQS). A portion of the V1V2 loop in the gp120 has been removed for clarity. c VH sequence (partial) alignment of UCA, intermediates (I8, I4, I2, I7), mature CH103 bnAbs (CH106, CH103), and lower branch mAbs (1A102RI6, 1AZCETI5) depict the mutations acquired during affinity maturation. Mutations of 14P to S and 30SS to GG (shown in red) in the FWR1 and HCDR1 proximal regions, respectively, were first observed in the intermediate I4 and maintained in each of the later evolving intermediates leading up to the mature bnAb CH103. Interestingly, these mutations were not observed in the lower branch antibodies (I7, 1A102RI6, 1AZCETI5) and binding to heterologous Env (B.63521) was orders of magnitude weaker compared to the mAbs of the CH103 bnAb branch (Supplementary Table 5). Asterisks mark residues that make direct contact with antigen

Back to article page