1yyl
From Proteopedia
(New page: 200px<br /> <applet load="1yyl" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yyl, resolution 2.75Å" /> '''crystal structure o...) |
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| - | [[Image:1yyl.gif|left|200px]]<br /> | + | [[Image:1yyl.gif|left|200px]]<br /><applet load="1yyl" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1yyl" size=" | + | |
caption="1yyl, resolution 2.75Å" /> | caption="1yyl, resolution 2.75Å" /> | ||
'''crystal structure of CD4M33, a scorpion-toxin mimic of CD4, in complex with HIV-1 YU2 gp120 envelope glycoprotein and anti-HIV-1 antibody 17b'''<br /> | '''crystal structure of CD4M33, a scorpion-toxin mimic of CD4, in complex with HIV-1 YU2 gp120 envelope glycoprotein and anti-HIV-1 antibody 17b'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The binding surface on CD4 for the HIV-1 gp120 envelope glycoprotein has | + | The binding surface on CD4 for the HIV-1 gp120 envelope glycoprotein has been transplanted previously onto a scorpion-toxin scaffold. Here, we use X-ray crystallography to characterize atomic-level details of gp120 with this transplant, CD4M33. Despite known envelope flexibility, the conformation of gp120 induced by CD4M33 was so similar to that induced by CD4 that localized measures were required to distinguish ligand-induced differences from lattice variation. To investigate relationships between structure, function, and mimicry, an F23 analog of CD4M33 was devised. Structural and thermodynamic analyses showed F23 to be a better molecular mimic of CD4 than CD4M33. F23 also showed increased neutralization breadth, against diverse isolates of HIV-1, HIV-2, and SIVcpz. Our results lend insight into the stability of the CD4 bound conformation of gp120, define measures that quantify molecular mimicry as a function of evolutionary distance, and suggest how such evaluations might be useful in developing mimetic antagonists with increased neutralization breadth. |
==About this Structure== | ==About this Structure== | ||
| - | 1YYL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with NAG and NDG as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1YYL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=NDG:'>NDG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YYL OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Barthe, P.]] | [[Category: Barthe, P.]] | ||
| - | [[Category: Decker, J | + | [[Category: Decker, J M.]] |
| - | [[Category: Hendrickson, W | + | [[Category: Hendrickson, W A.]] |
| - | [[Category: Huang, C | + | [[Category: Huang, C C.]] |
| - | [[Category: Kwong, P | + | [[Category: Kwong, P D.]] |
[[Category: Majeed, S.]] | [[Category: Majeed, S.]] | ||
[[Category: Martin, L.]] | [[Category: Martin, L.]] | ||
[[Category: Robinson, J.]] | [[Category: Robinson, J.]] | ||
[[Category: Roumestand, C.]] | [[Category: Roumestand, C.]] | ||
| - | [[Category: Shaw, G | + | [[Category: Shaw, G M.]] |
[[Category: Sodroski, J.]] | [[Category: Sodroski, J.]] | ||
[[Category: Stricher, F.]] | [[Category: Stricher, F.]] | ||
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[[Category: yu2]] | [[Category: yu2]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:10:24 2008'' |
Revision as of 14:10, 21 February 2008
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crystal structure of CD4M33, a scorpion-toxin mimic of CD4, in complex with HIV-1 YU2 gp120 envelope glycoprotein and anti-HIV-1 antibody 17b
Overview
The binding surface on CD4 for the HIV-1 gp120 envelope glycoprotein has been transplanted previously onto a scorpion-toxin scaffold. Here, we use X-ray crystallography to characterize atomic-level details of gp120 with this transplant, CD4M33. Despite known envelope flexibility, the conformation of gp120 induced by CD4M33 was so similar to that induced by CD4 that localized measures were required to distinguish ligand-induced differences from lattice variation. To investigate relationships between structure, function, and mimicry, an F23 analog of CD4M33 was devised. Structural and thermodynamic analyses showed F23 to be a better molecular mimic of CD4 than CD4M33. F23 also showed increased neutralization breadth, against diverse isolates of HIV-1, HIV-2, and SIVcpz. Our results lend insight into the stability of the CD4 bound conformation of gp120, define measures that quantify molecular mimicry as a function of evolutionary distance, and suggest how such evaluations might be useful in developing mimetic antagonists with increased neutralization breadth.
About this Structure
1YYL is a Single protein structure of sequence from Homo sapiens and Human immunodeficiency virus 1 with and as ligands. Full crystallographic information is available from OCA.
Reference
Scorpion-toxin mimics of CD4 in complex with human immunodeficiency virus gp120 crystal structures, molecular mimicry, and neutralization breadth., Huang CC, Stricher F, Martin L, Decker JM, Majeed S, Barthe P, Hendrickson WA, Robinson J, Roumestand C, Sodroski J, Wyatt R, Shaw GM, Vita C, Kwong PD, Structure. 2005 May;13(5):755-68. PMID:15893666
Page seeded by OCA on Thu Feb 21 16:10:24 2008
Categories: Homo sapiens | Human immunodeficiency virus 1 | Single protein | Barthe, P. | Decker, J M. | Hendrickson, W A. | Huang, C C. | Kwong, P D. | Majeed, S. | Martin, L. | Robinson, J. | Roumestand, C. | Shaw, G M. | Sodroski, J. | Stricher, F. | Vita, C. | Wyatt, R. | NAG | NDG | Antibody | Cd4 mimic | Cd4m33 | Gp120 | Hiv-1 | Scorpion toxin | Yu2
