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1akj
From Proteopedia
(New page: 200px<br /> <applet load="1akj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1akj, resolution 2.65Å" /> '''COMPLEX OF THE HUMA...) |
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==Overview== | ==Overview== | ||
The dimeric cell-surface glycoprotein CD8 is crucial to the positive, selection of cytotoxic T cells in the thymus. The homodimer, CD8alpha(alpha) or the heterodimer alpha beta stabilizes the interaction, of the T-cell antigen receptor (TCR) with major histocompatibility complex, (MHC) class I/peptide by binding to the class I molecule. Here we report, the crystal structure at 2.7 A resolution of a complex between, CD8alpha(alpha) and the human MHC molecule HLA-A2, which is associated, with peptide. CD8alpha(alpha) binds one HLA-A2/peptide molecule, interfacing with the alpha2 and alpha3 domains of HLA-A2 and also, contacting beta2-microglobulin. A flexible loop of the alpha3 domain, (residues 223-229) is clamped between the complementarity-determining, region (CDR)-like loops of the two CD8 subunits in the classic manner of, an antibody-antigen interaction, precluding the binding of a second MHC, molecule. The position of the alpha3 domain is different from that in, uncomplexed HLA-A2, being most similar to that in the TCR/Tax/HLA-A2, complex, but no conformational change extends to the MHC/peptide surface, presented for TCR recognition. Although these shifts in alpha3 may provide, a synergistic modulation of affinity, the binding of CD8 to MHC is clearly, consistent with an avidity-based contribution from CD8 to TCR-peptide-MHC, interactions. | The dimeric cell-surface glycoprotein CD8 is crucial to the positive, selection of cytotoxic T cells in the thymus. The homodimer, CD8alpha(alpha) or the heterodimer alpha beta stabilizes the interaction, of the T-cell antigen receptor (TCR) with major histocompatibility complex, (MHC) class I/peptide by binding to the class I molecule. Here we report, the crystal structure at 2.7 A resolution of a complex between, CD8alpha(alpha) and the human MHC molecule HLA-A2, which is associated, with peptide. CD8alpha(alpha) binds one HLA-A2/peptide molecule, interfacing with the alpha2 and alpha3 domains of HLA-A2 and also, contacting beta2-microglobulin. A flexible loop of the alpha3 domain, (residues 223-229) is clamped between the complementarity-determining, region (CDR)-like loops of the two CD8 subunits in the classic manner of, an antibody-antigen interaction, precluding the binding of a second MHC, molecule. The position of the alpha3 domain is different from that in, uncomplexed HLA-A2, being most similar to that in the TCR/Tax/HLA-A2, complex, but no conformational change extends to the MHC/peptide surface, presented for TCR recognition. Although these shifts in alpha3 may provide, a synergistic modulation of affinity, the binding of CD8 to MHC is clearly, consistent with an avidity-based contribution from CD8 to TCR-peptide-MHC, interactions. | ||
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| + | ==Disease== | ||
| + | Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142800 142800]], Ankylosing spondylitis, susceptibility to, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142800 142800]], Hypoproteinemia, hypercatabolic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109700 109700]], Megakaryoblastic leukemia, acute OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606078 606078]], Stevens-Johnson syndrome, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142800 142800]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: t-cell]] | [[Category: t-cell]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 15:59:22 2007'' |
Revision as of 13:52, 12 November 2007
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COMPLEX OF THE HUMAN MHC CLASS I GLYCOPROTEIN HLA-A2 AND THE T CELL CORECEPTOR CD8
Contents |
Overview
The dimeric cell-surface glycoprotein CD8 is crucial to the positive, selection of cytotoxic T cells in the thymus. The homodimer, CD8alpha(alpha) or the heterodimer alpha beta stabilizes the interaction, of the T-cell antigen receptor (TCR) with major histocompatibility complex, (MHC) class I/peptide by binding to the class I molecule. Here we report, the crystal structure at 2.7 A resolution of a complex between, CD8alpha(alpha) and the human MHC molecule HLA-A2, which is associated, with peptide. CD8alpha(alpha) binds one HLA-A2/peptide molecule, interfacing with the alpha2 and alpha3 domains of HLA-A2 and also, contacting beta2-microglobulin. A flexible loop of the alpha3 domain, (residues 223-229) is clamped between the complementarity-determining, region (CDR)-like loops of the two CD8 subunits in the classic manner of, an antibody-antigen interaction, precluding the binding of a second MHC, molecule. The position of the alpha3 domain is different from that in, uncomplexed HLA-A2, being most similar to that in the TCR/Tax/HLA-A2, complex, but no conformational change extends to the MHC/peptide surface, presented for TCR recognition. Although these shifts in alpha3 may provide, a synergistic modulation of affinity, the binding of CD8 to MHC is clearly, consistent with an avidity-based contribution from CD8 to TCR-peptide-MHC, interactions.
Disease
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142800], Ankylosing spondylitis, susceptibility to, 1 OMIM:[142800], Hypoproteinemia, hypercatabolic OMIM:[109700], Megakaryoblastic leukemia, acute OMIM:[606078], Stevens-Johnson syndrome, susceptibility to OMIM:[142800]
About this Structure
1AKJ is a Protein complex structure of sequences from Homo sapiens and Human immunodeficiency virus. Full crystallographic information is available from OCA.
Reference
Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2., Gao GF, Tormo J, Gerth UC, Wyer JR, McMichael AJ, Stuart DI, Bell JI, Jones EY, Jakobsen BK, Nature. 1997 Jun 5;387(6633):630-4. PMID:9177355
Page seeded by OCA on Mon Nov 12 15:59:22 2007
