1aqd: Difference between revisions
New page: left|200px<br /> <applet load="1aqd" size="450" color="white" frame="true" align="right" spinBox="true" caption="1aqd, resolution 2.45Å" /> '''HLA-DR1 (DRA, DRB1 ... |
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[[Image:1aqd.gif|left|200px]]<br /> | [[Image:1aqd.gif|left|200px]]<br /><applet load="1aqd" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1aqd, resolution 2.45Å" /> | caption="1aqd, resolution 2.45Å" /> | ||
'''HLA-DR1 (DRA, DRB1 0101) HUMAN CLASS II HISTOCOMPATIBILITY PROTEIN (EXTRACELLULAR DOMAIN) COMPLEXED WITH ENDOGENOUS PEPTIDE'''<br /> | '''HLA-DR1 (DRA, DRB1 0101) HUMAN CLASS II HISTOCOMPATIBILITY PROTEIN (EXTRACELLULAR DOMAIN) COMPLEXED WITH ENDOGENOUS PEPTIDE'''<br /> | ||
==Overview== | ==Overview== | ||
BACKGROUND: Class II major histocompatibility complex (MHC) proteins are | BACKGROUND: Class II major histocompatibility complex (MHC) proteins are cell surface glycoproteins that bind peptides and present them to T cells as part of the mechanism for detecting and responding to foreign material in the body. The peptide-binding activity exhibits allele-specific preferences for particular sidechains at some positions, although the structural basis of these preferences is not understood in detail. We have determined the 2.45 A crystal structure of the human class II MHC protein HLA-DR1 in complex with the tight binding endogenous peptide A2 (103-117) in order to discover peptide-MHC interactions that are important in determining the binding motif and to investigate conformational constraints on the bound peptide. RESULTS: The bound peptide adopts a polyproline II-like conformation and places several sidechains within pockets in the binding site. Bound water molecules mediate MHC-peptide contacts at several sites. A tryptophan residue from the beta 2 'lower' domain of HLA-DR1 was found to project into a pocket underneath the peptide-binding domain and may be important in modulating interdomain interactions in MHC proteins. CONCLUSIONS: The peptide-binding motif of HLA-DR1 includes an aromatic residue at position +1, an arginine residue at position +2, and a small residue at position +6 (where the numbering refers to the normal MHC class II convention); these preferences can be understood in light of interactions observed in the peptide-MHC complex. Comparison of the structure with that of another MHC-peptide complex shows that completely different peptide sequences bind in essentially the same conformation and are accommodated with only minimal rearrangement of HLA-DR1 residues. Small conformational differences that are observed appear to be important in interactions with other proteins. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1AQD is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | 1AQD is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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=1AQD OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Murthy, V | [[Category: Murthy, V L.]] | ||
[[Category: Stern, L | [[Category: Stern, L J.]] | ||
[[Category: complex (mhc protein/antigen)]] | [[Category: complex (mhc protein/antigen)]] | ||
[[Category: histocompatibility antigen]] | [[Category: histocompatibility antigen]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:47:11 2008'' | ||
Revision as of 12:47, 21 February 2008
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HLA-DR1 (DRA, DRB1 0101) HUMAN CLASS II HISTOCOMPATIBILITY PROTEIN (EXTRACELLULAR DOMAIN) COMPLEXED WITH ENDOGENOUS PEPTIDE
OverviewOverview
BACKGROUND: Class II major histocompatibility complex (MHC) proteins are cell surface glycoproteins that bind peptides and present them to T cells as part of the mechanism for detecting and responding to foreign material in the body. The peptide-binding activity exhibits allele-specific preferences for particular sidechains at some positions, although the structural basis of these preferences is not understood in detail. We have determined the 2.45 A crystal structure of the human class II MHC protein HLA-DR1 in complex with the tight binding endogenous peptide A2 (103-117) in order to discover peptide-MHC interactions that are important in determining the binding motif and to investigate conformational constraints on the bound peptide. RESULTS: The bound peptide adopts a polyproline II-like conformation and places several sidechains within pockets in the binding site. Bound water molecules mediate MHC-peptide contacts at several sites. A tryptophan residue from the beta 2 'lower' domain of HLA-DR1 was found to project into a pocket underneath the peptide-binding domain and may be important in modulating interdomain interactions in MHC proteins. CONCLUSIONS: The peptide-binding motif of HLA-DR1 includes an aromatic residue at position +1, an arginine residue at position +2, and a small residue at position +6 (where the numbering refers to the normal MHC class II convention); these preferences can be understood in light of interactions observed in the peptide-MHC complex. Comparison of the structure with that of another MHC-peptide complex shows that completely different peptide sequences bind in essentially the same conformation and are accommodated with only minimal rearrangement of HLA-DR1 residues. Small conformational differences that are observed appear to be important in interactions with other proteins.
DiseaseDisease
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142800], Ankylosing spondylitis, susceptibility to, 1 OMIM:[142800], Stevens-Johnson syndrome, susceptibility to OMIM:[142800]
About this StructureAbout this Structure
1AQD is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The class II MHC protein HLA-DR1 in complex with an endogenous peptide: implications for the structural basis of the specificity of peptide binding., Murthy VL, Stern LJ, Structure. 1997 Oct 15;5(10):1385-96. PMID:9351812
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