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1jl4

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[[Image:1jl4.jpg|left|200px]]<br /><applet load="1jl4" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1jl4, resolution 4.3&Aring;" />
 
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'''CRYSTAL STRUCTURE OF THE HUMAN CD4 N-TERMINAL TWO DOMAIN FRAGMENT COMPLEXED TO A CLASS II MHC MOLECULE'''<br />
 
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==Overview==
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==CRYSTAL STRUCTURE OF THE HUMAN CD4 N-TERMINAL TWO DOMAIN FRAGMENT COMPLEXED TO A CLASS II MHC MOLECULE==
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The structural basis of the interaction between the CD4 coreceptor and a, class II major histocompatibility complex (MHC) is described. The crystal, structure of a complex containing the human CD4 N-terminal two-domain, fragment and the murine I-A(k) class II MHC molecule with associated, peptide (pMHCII) shows that only the "top corner" of the CD4 molecule, directly contacts pMHCII. The CD4 Phe-43 side chain extends into a, hydrophobic concavity formed by MHC residues from both alpha 2 and beta 2, domains. A ternary model of the CD4-pMHCII-T-cell receptor (TCR) reveals, that the complex appears V-shaped with the membrane-proximal pMHCII at the, apex. This configuration excludes a direct TCR-CD4 interaction and, suggests how TCR and CD4 signaling is coordinated around the antigenic, pMHCII complex. Human CD4 binds to HIV gp120 in a manner strikingly, similar to the way in which CD4 interacts with pMHCII. Additional contacts, between gp120 and CD4 give the CD4-gp120 complex a greater affinity. Thus, ligation of the viral envelope glycoprotein to CD4 occludes the, pMHCII-binding site on CD4, contributing to immunodeficiency.
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<StructureSection load='1jl4' size='340' side='right'caption='[[1jl4]], [[Resolution|resolution]] 4.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1jl4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. The March 2005 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''T-Cell Receptor'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2005_3 10.2210/rcsb_pdb/mom_2005_3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JL4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JL4 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.3&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1jl4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jl4 OCA], [https://pdbe.org/1jl4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jl4 RCSB], [https://www.ebi.ac.uk/pdbsum/1jl4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jl4 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/HA2K_MOUSE HA2K_MOUSE]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jl/1jl4_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1jl4 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The structural basis of the interaction between the CD4 coreceptor and a class II major histocompatibility complex (MHC) is described. The crystal structure of a complex containing the human CD4 N-terminal two-domain fragment and the murine I-A(k) class II MHC molecule with associated peptide (pMHCII) shows that only the "top corner" of the CD4 molecule directly contacts pMHCII. The CD4 Phe-43 side chain extends into a hydrophobic concavity formed by MHC residues from both alpha 2 and beta 2 domains. A ternary model of the CD4-pMHCII-T-cell receptor (TCR) reveals that the complex appears V-shaped with the membrane-proximal pMHCII at the apex. This configuration excludes a direct TCR-CD4 interaction and suggests how TCR and CD4 signaling is coordinated around the antigenic pMHCII complex. Human CD4 binds to HIV gp120 in a manner strikingly similar to the way in which CD4 interacts with pMHCII. Additional contacts between gp120 and CD4 give the CD4-gp120 complex a greater affinity. Thus, ligation of the viral envelope glycoprotein to CD4 occludes the pMHCII-binding site on CD4, contributing to immunodeficiency.
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==Disease==
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Crystal structure of the human CD4 N-terminal two-domain fragment complexed to a class II MHC molecule.,Wang JH, Meijers R, Xiong Y, Liu JH, Sakihama T, Zhang R, Joachimiak A, Reinherz EL Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10799-804. Epub 2001 Sep 4. PMID:11535811<ref>PMID:11535811</ref>
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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]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1JL4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus], [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JL4 OCA].
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</div>
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<div class="pdbe-citations 1jl4" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Crystal structure of the human CD4 N-terminal two-domain fragment complexed to a class II MHC molecule., Wang JH, Meijers R, Xiong Y, Liu JH, Sakihama T, Zhang R, Joachimiak A, Reinherz EL, Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10799-804. Epub 2001 Sep 4. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11535811 11535811]
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*[[CD4 3D structures|CD4 3D structures]]
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*[[MHC 3D structures|MHC 3D structures]]
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*[[MHC II 3D structures|MHC II 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Gallus gallus]]
[[Category: Gallus gallus]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Protein complex]]
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[[Category: RCSB PDB Molecule of the Month]]
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[[Category: Meijers, R.]]
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[[Category: T-Cell Receptor]]
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[[Category: Reinherz, E.L.]]
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[[Category: Meijers R]]
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[[Category: Wang, J.H.]]
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[[Category: Reinherz EL]]
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[[Category: protein-protein complex]]
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[[Category: Wang J-H]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:07:54 2008''
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Current revision

CRYSTAL STRUCTURE OF THE HUMAN CD4 N-TERMINAL TWO DOMAIN FRAGMENT COMPLEXED TO A CLASS II MHC MOLECULE

PDB ID 1jl4

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