In this study, we test our hypothesis that CD4-induced (CD4i) antibodies, which target the CoRbs, could also induce conformational changes in gp120 leading to better exposed conserved neutralizing antibody epitopes including the CD4-binding site (CD4bs). We found that a mixture of CD4i antibodies with gp120 only weakly enhanced CD4 binding.

In this study, we designed gp120-CD4i fusion protein as immunogens to improve the elicitation of CD4bs bNAb response by selective elimination of glycans flanking the CD4bs to increase the CD4bs exposure while blocking the immunodominant non-bNAb epitopes by including CD4i mAb functional moieties as immunogen component.

Here we report the crystal structure at 2.5 Å resolution of a partially deglycosylated HIV-1 gp120 core bound to a two-domain fragment of the CD4 cellular receptor and to the antigen-binding fragment (Fab) of an antibody, 17b, that is directed against a CD4i epitope.

2010年3月31日 · We present a crystal structure containing a clade C gp120 envelope. The structure, a complex between gp120, the host receptor CD4 and the CD4-induced antibody 21c, reveals that the 21c epitope...

2019年1月3日 · In a recent online article of Nature, Shaik et al. solved the cryo-electron microscopy (cryo-EM) structure of a full-length monomeric gp120 in complex with a soluble CD4 ectodomain and an unmodified human CCR5 reconstituted into a lipid micelle [3].

CD4 binding locks the gp120 core into a conformation that is competent for chemokine receptor binding and is recognized by CD4i antibodies. This conformational transition occurs on the pathway to virus entry. CD4BS antibodies bind free gp120 and restrict its ability to assume the CD4-bound conformation, thus disrupting the entry process.

2020年3月15日 · In this study, we designed a panel of novel immunogens that 1) preferentially expose the CD4bs by selective elimination of glycosylation sites flanking the CD4bs, and 2) minimize the nND immune response by engineering fusion proteins consisting of gp120 Core and one or two CD4-induced (CD4i) mAbs for masking nND epitopes, referred to as gp120 ...

2023年11月22日 · When bound to two CD4s, the CD4-bound gp120s exhibited an open Env conformation including a four-stranded gp120 bridging sheet and displaced gp120 V1V2 loops that expose the coreceptor sites on...

1998年6月18日 · We have solved the X-ray crystal structure at 2.5 Å resolution of an HIV-1 gp120 core complexed with a two-domain fragment of human CD4 and an antigen-binding fragment of a neutralizing antibody...

2020年3月15日 · In this study, we designed gp120–CD4i fusion protein as immunogens to improve the elicitation of CD4bs bNAb response by selective elimination of glycans flanking the CD4bs to increase the CD4bs exposure while blocking the immunodominant non-bNAb epitopes by including CD4i mAb functional moieties as immunogen component.