VRC01 gp120 complex: Difference between revisions
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<scene name='52/521911/Cv/3'>VRC01 heavy chain (gold, green, magenta, blue), light chain (aqua, pink, cyan, rust) in complex with gp120 (red, grey, yellow, wheat)</scene> ([[3ngb]]). | <scene name='52/521911/Cv/3'>VRC01 heavy chain (gold, green, magenta, blue), light chain (aqua, pink, cyan, rust) in complex with gp120 (red, grey, yellow, wheat)</scene> ([[3ngb]]). | ||
<u>Similarities to CD4 in complex with gp120</u>. Analysis of VRC01 in complex with gp120 shows that this complex covers 98% of the CD4 binding site. However, VRC01’s binding site extends outside that of CD4, making it vulnerable to resistance of VRC01 neutralization by antigenic variation<ref name="zhou">PMID: 20616231</ref>. [[Image: Target Site.jpg | thumb | alt=text | Picture 1]] In Picture 1B, the contact surface of VRC01 and CD4 are shown on gp120. The green represents VRC01's contact surface and yellow represents CD4's contact surface<ref name="kwong" />. Both the heavy chain and light chain of VRC01 contribute to the contact surfaces of the VRC01 gp120 complex. The focus of the binding is on the heavy chain second complementary-determining region. Over 50% of the surface contact involves the heavy chain second complementary-determining region; this is similar to CD4’s interaction with gp120. Two dominant residues, Phe43 and Arg59, are involved in CD4’s binding to gp120. Of these two residues, only the arginine interaction is mimicked by VRC01. This dominant interaction is between Asp368 of gp120 and Arg59 of the CD4 receptor and between Asp368 of gp120 and Arg71 of VRC01. Arg71 and Asp368 form a <scene name='VRC01_gp120_complex/Salt_bridge/1'>salt bridge</scene><ref name="zhou" />. | <u>Similarities to CD4 in complex with gp120</u>. Analysis of VRC01 in complex with gp120 shows that this complex covers 98% of the CD4 binding site. However, VRC01’s binding site extends outside that of CD4, making it vulnerable to resistance of VRC01 neutralization by antigenic variation<ref name="zhou">PMID: 20616231</ref>. | ||
[[Image: Target Site.jpg | thumb | alt=text | Picture 1]] | |||
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In Picture 1B, the contact surface of VRC01 and CD4 are shown on gp120. The green represents VRC01's contact surface and yellow represents CD4's contact surface<ref name="kwong" />. Both the heavy chain and light chain of VRC01 contribute to the contact surfaces of the VRC01 gp120 complex. The focus of the binding is on the heavy chain second complementary-determining region. Over 50% of the surface contact involves the heavy chain second complementary-determining region; this is similar to CD4’s interaction with gp120. Two dominant residues, Phe43 and Arg59, are involved in CD4’s binding to gp120. Of these two residues, only the arginine interaction is mimicked by VRC01. This dominant interaction is between Asp368 of gp120 and Arg59 of the CD4 receptor and between Asp368 of gp120 and Arg71 of VRC01. Arg71 and Asp368 form a <scene name='VRC01_gp120_complex/Salt_bridge/1'>salt bridge</scene><ref name="zhou" />. | |||
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<u>Other features</u>. VRC01 light chain residues, <scene name='VRC01_gp120_complex/Tyr_28_and_ser_30/1'>Tyr28 and Ser30</scene>, make contacts with the protein-proximal N-acetyl-glucosamine from the N-linked glycan residue 276 of gp120. While other structures are blocked from binding because glycan shielding, VRC01 takes advantage of the glycan for binding<ref name="zhou" />. | <u>Other features</u>. VRC01 light chain residues, <scene name='VRC01_gp120_complex/Tyr_28_and_ser_30/1'>Tyr28 and Ser30</scene>, make contacts with the protein-proximal N-acetyl-glucosamine from the N-linked glycan residue 276 of gp120. While other structures are blocked from binding because glycan shielding, VRC01 takes advantage of the glycan for binding<ref name="zhou" />. | ||
==HIV Prevention Research== | ==HIV Prevention Research== | ||
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A similar experiment was done in 2012; it used humanized mouse models called RAG-hu mice, which contained human target cells. Results show that seven out of nine mice that were administered the VRC01 antibody and all mice that were given a cocktail containing four broadly neutralizing antibodies as a topical gel were protected against HIV-1. These results showed that broadly neutralizing antibodies could be used as a topical microbicide to prevent vaginal transmission of HIV and that a combination of antibodies can provide better protection against HIV. When the VRC01 antibody and the broadly neutralizing antibody cocktail were administered to the humanized mice via the intravenous route, none of the mice were infected with SHIV<ref>PMID: 22832125</ref>. | A similar experiment was done in 2012; it used humanized mouse models called RAG-hu mice, which contained human target cells. Results show that seven out of nine mice that were administered the VRC01 antibody and all mice that were given a cocktail containing four broadly neutralizing antibodies as a topical gel were protected against HIV-1. These results showed that broadly neutralizing antibodies could be used as a topical microbicide to prevent vaginal transmission of HIV and that a combination of antibodies can provide better protection against HIV. When the VRC01 antibody and the broadly neutralizing antibody cocktail were administered to the humanized mice via the intravenous route, none of the mice were infected with SHIV<ref>PMID: 22832125</ref>. | ||
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==References== | ==References== | ||
<references /> | <references /> | ||
