VRC01 gp120 complex: Difference between revisions
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<u>Similarities to other antibodies in complex with gp120</u>. Although only about 50% of the amino acids in the variable region of the heavy chains of different CD4 binding site antibodies were conserved, the structures of each of their complex with gp120 was similar. Comparison between other CD4 binding site antibodies show that the Arg71 and Asp368 interaction is also conserved. From sequence analysis of 10 antibodies of the same IGHV1-2*02 germline, 70-90 nucleotide changes are made. Only two residues changes from this germline mature into the same amino acids. These changes occur in a hydrophobic contact of the heavy chain second complementary-determining region. The two amino acid changes are Gly56 into Ala56 and Thr57 into Val57<ref name="wu" />. More hydrophobic residues at this position led to an increased potency and breadth by increasing contacts with gp120’s bridging domain<ref>PMID: 22033520</ref>. Another conserved interaction is the interaction of Tyr91 and Glu96 of VRC01 with loop D of gp120. These residues engage loop D by polar interactions<ref name="scheid">PMID: 21764753</ref>. | <u>Similarities to other antibodies in complex with gp120</u>. Although only about 50% of the amino acids in the variable region of the heavy chains of different CD4 binding site antibodies were conserved, the structures of each of their complex with gp120 was similar. Comparison between other CD4 binding site antibodies show that the Arg71 and Asp368 interaction is also conserved. From sequence analysis of 10 antibodies of the same IGHV1-2*02 germline, 70-90 nucleotide changes are made. Only two residues changes from this germline mature into the same amino acids. These changes occur in a hydrophobic contact of the heavy chain second complementary-determining region. The two amino acid changes are Gly56 into Ala56 and Thr57 into Val57<ref name="wu" />. More <scene name='VRC01_gp120_complex/Hydrophobic_residues/2'>hydrophobic residues</scene> at this position led to an increased potency and breadth by increasing contacts with gp120’s bridging domain<ref>PMID: 22033520</ref>. Another conserved interaction is the interaction of Tyr91 and Glu96 of VRC01 with loop D of gp120. These residues engage loop D by polar interactions<ref name="scheid">PMID: 21764753</ref>. | ||
Also, when 10 best antibody sequences were aligned, it was found that 68 heavy chain residues were conserved and 7 of these residues were involved in the contact between VRC01 and gp120. In comparison only 53 light chain residues were conserved and only 3 of these residues were involved in the contact between VRC01 and gp120. This is consistent with other research that has shown the light chain of VRC01 having a limited role in attachment to gp120 in comparison to the heavy chain<ref name="scheid" />. | Also, when 10 best antibody sequences were aligned, it was found that 68 heavy chain residues were conserved and 7 of these residues were involved in the contact between VRC01 and gp120. In comparison only 53 light chain residues were conserved and only 3 of these residues were involved in the contact between VRC01 and gp120. This is consistent with other research that has shown the light chain of VRC01 having a limited role in attachment to gp120 in comparison to the heavy chain<ref name="scheid" />. | ||
