1cdy: Difference between revisions
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[[Image:1cdy.gif|left|200px]]<br /> | [[Image:1cdy.gif|left|200px]]<br /><applet load="1cdy" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1cdy" size=" | |||
caption="1cdy, resolution 2.0Å" /> | caption="1cdy, resolution 2.0Å" /> | ||
'''STRUCTURE OF T-CELL SURFACE GLYCOPROTEIN CD4 MUTANT WITH GLY 47 REPLACED BY SER'''<br /> | '''STRUCTURE OF T-CELL SURFACE GLYCOPROTEIN CD4 MUTANT WITH GLY 47 REPLACED BY SER'''<br /> | ||
==Overview== | ==Overview== | ||
The T-cell antigen coreceptor CD4 also serves as the receptor for the | The T-cell antigen coreceptor CD4 also serves as the receptor for the envelope glycoprotein gp120 of HIV. Extensive mutational analysis of CD4 has implicated residues from a portion of the extracellular amino-terminal domain (D1) in gp120 binding. However, none of these proteins has been fully characterized biophysically, and thus the precise effects on molecular structure and binding interactions are unknown. In the present study, we produced soluble versions of three mutant CD4 molecules (F43V, G47S, and A55F) and characterized their structural properties, thermostability, and ability to bind gp120. Crystallographic and thermodynamic analysis showed minimal structural alterations in the F43V and G47S mutant proteins, which have solvent-exposed mutant side chains. In contrast, some degree of disorder appears to exist in the folded state of A55F, as a result of mutating a buried side chain. Real time kinetic measurements of the interaction of the mutant proteins with gp120 showed affinity decreases of 5-fold for G47S, 50-fold for A55F, and 200-fold for F43V. Although both rate constants for the binding reaction were affected by these mutations, the loss in affinity was mainly due to a decrease in on rates, with less drastic changes occurring in the off rates. These observations suggest the involvement of conformational adaptation in the CD4-gp120 interaction. Together, the structural and kinetic data confirm that F43V is a critical residue in gp120 recognition site, which may also include main chain interactions at residue Gly-47. | ||
==Disease== | |||
Known diseases associated with this structure: CD4 lymphocyte deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=186940 186940]], Lupus erythematosus, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=186940 186940]] | |||
==About this Structure== | ==About this Structure== | ||
1CDY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | 1CDY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence 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=1CDY OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Brouillette, C | [[Category: Brouillette, C G.]] | ||
[[Category: Chaiken, I | [[Category: Chaiken, I M.]] | ||
[[Category: Hendrickson, W | [[Category: Hendrickson, W A.]] | ||
[[Category: Myszka, D.]] | [[Category: Myszka, D.]] | ||
[[Category: Sweet, R | [[Category: Sweet, R W.]] | ||
[[Category: Tendian, S | [[Category: Tendian, S W.]] | ||
[[Category: Wu, H.]] | [[Category: Wu, H.]] | ||
[[Category: glycoprotein]] | [[Category: glycoprotein]] | ||
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[[Category: transmembrane]] | [[Category: transmembrane]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:05:06 2008'' | ||