1jl4: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1jl4. | [[Image:1jl4.jpg|left|200px]]<br /><applet load="1jl4" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1jl4" size=" | |||
caption="1jl4, resolution 4.3Å" /> | caption="1jl4, resolution 4.3Å" /> | ||
'''CRYSTAL STRUCTURE OF THE HUMAN CD4 N-TERMINAL TWO DOMAIN FRAGMENT COMPLEXED TO A CLASS II MHC MOLECULE'''<br /> | '''CRYSTAL STRUCTURE OF THE HUMAN CD4 N-TERMINAL TWO DOMAIN FRAGMENT COMPLEXED TO A CLASS II MHC MOLECULE'''<br /> | ||
| Line 6: | Line 5: | ||
==Overview== | ==Overview== | ||
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. | 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. | ||
==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== | ||
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:// | 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]. | ||
==Reference== | ==Reference== | ||
| Line 21: | Line 23: | ||
[[Category: protein-protein complex]] | [[Category: protein-protein complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:07:54 2008'' | ||