1a9b: Difference between revisions
New page: left|200px<br /> <applet load="1a9b" size="450" color="white" frame="true" align="right" spinBox="true" caption="1a9b, resolution 3.2Å" /> '''DECAMER-LIKE CONFORM... |
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[[Image:1a9b.gif|left|200px]]<br /> | [[Image:1a9b.gif|left|200px]]<br /><applet load="1a9b" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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'''DECAMER-LIKE CONFORMATION OF A NANO-PEPTIDE BOUND TO HLA-B3501 DUE TO NONSTANDARD POSITIONING OF THE C-TERMINUS'''<br /> | '''DECAMER-LIKE CONFORMATION OF A NANO-PEPTIDE BOUND TO HLA-B3501 DUE TO NONSTANDARD POSITIONING OF THE C-TERMINUS'''<br /> | ||
==Overview== | ==Overview== | ||
The N and C termini of peptides presented by major histocompatibility | The N and C termini of peptides presented by major histocompatibility complex (MHC) class I molecules are held within the peptide binding groove by a network of hydrogen bonds to conserved MHC residues. However, the published structure of the human allele HLA-B*3501 complexed with the nef octa-peptide VPLRPMTY, revealed non-standard positioning for both peptide termini. To investigate whether these deviations are indeed related to the length of the nef-peptide, we have determined the structure of HLA-B*3501 presenting a nona-peptide to 2.5 A resolution. A comparison of HLA-B*3501/peptide complexes with structures of other HLA molecules exhibits allele-specific properties of HLA-B*3501, as well as peptide-induced structural changes. Independent of the length of the bound peptide, HLA-B*3501 positions the peptide C terminus significantly closer to the alpha1-helix and nearer to the A pocket than observed for other HLA class I/peptide complexes. This reorientation is accompanied by a shift within the N-terminal part of the alpha2-helix towards the middle of the binding groove. Due to the short distance between the N and C termini, the nona-peptide is compressed and forced to zig-zag vertically within the binding groove. Its conformation rather resembles that of a deca-peptide than of other nona-peptides bound to class I molecules. Superposition of both HLA-B*3501/peptide complexes additionally reveals a significant, peptide-dependent deviation between the N-terminal parts of the alpha1-helices which might be due to different positioning of the peptide N termini. Taken together, these data illustrate the strong interdependence between the HLA class I molecule and the bound peptide. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1A9B 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:// | 1A9B 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=1A9B OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: mhc class i]] | [[Category: mhc class i]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:42:20 2008'' | ||
Revision as of 12:42, 21 February 2008
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DECAMER-LIKE CONFORMATION OF A NANO-PEPTIDE BOUND TO HLA-B3501 DUE TO NONSTANDARD POSITIONING OF THE C-TERMINUS
OverviewOverview
The N and C termini of peptides presented by major histocompatibility complex (MHC) class I molecules are held within the peptide binding groove by a network of hydrogen bonds to conserved MHC residues. However, the published structure of the human allele HLA-B*3501 complexed with the nef octa-peptide VPLRPMTY, revealed non-standard positioning for both peptide termini. To investigate whether these deviations are indeed related to the length of the nef-peptide, we have determined the structure of HLA-B*3501 presenting a nona-peptide to 2.5 A resolution. A comparison of HLA-B*3501/peptide complexes with structures of other HLA molecules exhibits allele-specific properties of HLA-B*3501, as well as peptide-induced structural changes. Independent of the length of the bound peptide, HLA-B*3501 positions the peptide C terminus significantly closer to the alpha1-helix and nearer to the A pocket than observed for other HLA class I/peptide complexes. This reorientation is accompanied by a shift within the N-terminal part of the alpha2-helix towards the middle of the binding groove. Due to the short distance between the N and C termini, the nona-peptide is compressed and forced to zig-zag vertically within the binding groove. Its conformation rather resembles that of a deca-peptide than of other nona-peptides bound to class I molecules. Superposition of both HLA-B*3501/peptide complexes additionally reveals a significant, peptide-dependent deviation between the N-terminal parts of the alpha1-helices which might be due to different positioning of the peptide N termini. Taken together, these data illustrate the strong interdependence between the HLA class I molecule and the bound peptide.
DiseaseDisease
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142830], Hypoproteinemia, hypercatabolic OMIM:[109700], Spondyloarthropathy, susceptibility to, 1 OMIM:[142830], Stevens-Johnson syndrome, carbamazepine-induced, susceptibility to OMIM:[142830]
About this StructureAbout this Structure
1A9B is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Decamer-like conformation of a nona-peptide bound to HLA-B*3501 due to non-standard positioning of the C terminus., Menssen R, Orth P, Ziegler A, Saenger W, J Mol Biol. 1999 Jan 15;285(2):645-53. PMID:9878435
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