1zls
From Proteopedia
(New page: 200px<br /> <applet load="1zls" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zls, resolution 2.001Å" /> '''FAB 2G12 + Man4'''...) |
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| - | [[Image:1zls.gif|left|200px]]<br /> | + | [[Image:1zls.gif|left|200px]]<br /><applet load="1zls" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1zls" size=" | + | |
caption="1zls, resolution 2.001Å" /> | caption="1zls, resolution 2.001Å" /> | ||
'''FAB 2G12 + Man4'''<br /> | '''FAB 2G12 + Man4'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Human antibody 2G12 neutralizes a broad range of HIV-1 isolates. Hence, molecular characterization of its epitope, which corresponds to a | + | Human antibody 2G12 neutralizes a broad range of HIV-1 isolates. Hence, molecular characterization of its epitope, which corresponds to a conserved cluster of oligomannoses on the viral envelope glycoprotein gp120, is a high priority in HIV vaccine design. A prior crystal structure of 2G12 in complex with Man(9)GlcNAc(2) highlighted the central importance of the D1 arm in antibody binding. To characterize the specificity of 2G12 more precisely, we performed solution-phase ELISA, carbohydrate microarray analysis, and cocrystallized Fab 2G12 with four different oligomannose derivatives (Man(4), Man(5), Man(7), and Man(8)) that compete with gp120 for binding to 2G12. Our combined studies reveal that 2G12 is capable of binding both the D1 and D3 arms of the Man(9)GlcNAc(2) moiety, which would provide more flexibility to make the required multivalent interactions between the antibody and the gp120 oligomannose cluster than thought previously. These results have important consequences for the design of immunogens to elicit 2G12-like neutralizing antibodies as a component of an HIV vaccine. |
==About this Structure== | ==About this Structure== | ||
| - | 1ZLS is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1ZLS is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZLS OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Astronomo, R | + | [[Category: Astronomo, R D.]] |
| - | [[Category: Best, M | + | [[Category: Best, M D.]] |
| - | [[Category: Burton, D | + | [[Category: Burton, D R.]] |
| - | [[Category: Calarese, D | + | [[Category: Calarese, D A.]] |
| - | [[Category: Lee, H | + | [[Category: Lee, H K.]] |
| - | [[Category: Stanfield, R | + | [[Category: Stanfield, R L.]] |
| - | [[Category: Wilson, I | + | [[Category: Wilson, I A.]] |
| - | [[Category: Wong, C | + | [[Category: Wong, C H.]] |
[[Category: hiv neutralizing antibody; anti-carbohydrate; domain-swapping]] | [[Category: hiv neutralizing antibody; anti-carbohydrate; domain-swapping]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:16:48 2008'' |
Revision as of 14:16, 21 February 2008
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FAB 2G12 + Man4
Overview
Human antibody 2G12 neutralizes a broad range of HIV-1 isolates. Hence, molecular characterization of its epitope, which corresponds to a conserved cluster of oligomannoses on the viral envelope glycoprotein gp120, is a high priority in HIV vaccine design. A prior crystal structure of 2G12 in complex with Man(9)GlcNAc(2) highlighted the central importance of the D1 arm in antibody binding. To characterize the specificity of 2G12 more precisely, we performed solution-phase ELISA, carbohydrate microarray analysis, and cocrystallized Fab 2G12 with four different oligomannose derivatives (Man(4), Man(5), Man(7), and Man(8)) that compete with gp120 for binding to 2G12. Our combined studies reveal that 2G12 is capable of binding both the D1 and D3 arms of the Man(9)GlcNAc(2) moiety, which would provide more flexibility to make the required multivalent interactions between the antibody and the gp120 oligomannose cluster than thought previously. These results have important consequences for the design of immunogens to elicit 2G12-like neutralizing antibodies as a component of an HIV vaccine.
About this Structure
1ZLS is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Dissection of the carbohydrate specificity of the broadly neutralizing anti-HIV-1 antibody 2G12., Calarese DA, Lee HK, Huang CY, Best MD, Astronomo RD, Stanfield RL, Katinger H, Burton DR, Wong CH, Wilson IA, Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13372-7. Epub 2005 Sep 7. PMID:16174734
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