1cdu: Difference between revisions
No edit summary |
No edit summary |
||
| (18 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==STRUCTURE OF T-CELL SURFACE GLYCOPROTEIN CD4 MUTANT WITH PHE 43 REPLACED BY VAL== | ||
The T-cell antigen coreceptor CD4 also serves as the receptor for the | <StructureSection load='1cdu' size='340' side='right'caption='[[1cdu]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1cdu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CDU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CDU FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1cdu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cdu OCA], [https://pdbe.org/1cdu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cdu RCSB], [https://www.ebi.ac.uk/pdbsum/1cdu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cdu ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CD4_HUMAN CD4_HUMAN] Accessory protein for MHC class-II antigen/T-cell receptor interaction. May regulate T-cell activation. Induces the aggregation of lipid rafts. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cd/1cdu_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1cdu ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
Kinetic and structural analysis of mutant CD4 receptors that are defective in HIV gp120 binding.,Wu H, Myszka DG, Tendian SW, Brouillette CG, Sweet RW, Chaiken IM, Hendrickson WA Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15030-5. PMID:8986758<ref>PMID:8986758</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1cdu" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[CD4 3D structures|CD4 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Brouillette | [[Category: Brouillette CG]] | ||
[[Category: Chaiken | [[Category: Chaiken IM]] | ||
[[Category: Hendrickson | [[Category: Hendrickson WA]] | ||
[[Category: Myszka | [[Category: Myszka D]] | ||
[[Category: Sweet | [[Category: Sweet RW]] | ||
[[Category: Tendian | [[Category: Tendian SW]] | ||
[[Category: Wu | [[Category: Wu H]] | ||
Latest revision as of 11:22, 6 November 2024
STRUCTURE OF T-CELL SURFACE GLYCOPROTEIN CD4 MUTANT WITH PHE 43 REPLACED BY VALSTRUCTURE OF T-CELL SURFACE GLYCOPROTEIN CD4 MUTANT WITH PHE 43 REPLACED BY VAL
Structural highlights
FunctionCD4_HUMAN Accessory protein for MHC class-II antigen/T-cell receptor interaction. May regulate T-cell activation. Induces the aggregation of lipid rafts. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. Kinetic and structural analysis of mutant CD4 receptors that are defective in HIV gp120 binding.,Wu H, Myszka DG, Tendian SW, Brouillette CG, Sweet RW, Chaiken IM, Hendrickson WA Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15030-5. PMID:8986758[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
| ||||||||||||||||