PDBsum entry 1t5x

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Immune system PDB id
Protein chains
179 a.a. *
190 a.a. *
13 a.a. *
230 a.a. *
Waters ×221
* Residue conservation analysis

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Key reference
Title A polymorphic pocket at the p10 position contributes to peptide binding specificity in class ii mhc proteins.
Authors Z.Zavala-Ruiz, I.Strug, M.W.Anderson, J.Gorski, L.J.Stern.
Ref. Chem Biol, 2004, 11, 1395-1402. [DOI no: 10.1016/j.chembiol.2004.08.007]
PubMed id 15489166
Peptides bind to class II major histocompatibility complex (MHC) proteins in an extended conformation. Pockets in the peptide binding site spaced to accommodate peptide side chains at the P1, P4, P6, and P9 positions have been previously characterized and help to explain the obtained peptide binding specificity. However, two peptides differing only at P10 have significantly different binding affinities for HLA-DR1. The structure of HLA-DR1 in complex with the tighter binding peptide shows that the peptide binds in the usual polyproline type II conformation, but with the P10 residue accommodated in a shallow pocket at the end of the binding groove. HLA-DR1 variants with polymorphic residues at these positions were produced and found to exhibit different side chain specificity at the P10 position. These results define a new specificity position in HLA-DR proteins.
Figure 1.
Figure 1. The P10 Position of Peptides Can Affect Binding to HLA-DR1(A) Surface of the HLA-DR1 peptide binding site with bound AAYSDQATPLLLSPR peptide shown as a stick model. In the peptide, carbon atoms are yellow, nitrogen atoms are blue, and oxygen atoms are red. Peptide side chain binding pockets are labeled.(B) Competitive binding analysis of two peptides that differ only in the P10 position. A fixed concentration of peptide-free HLA-DR1 and biotinylated Ha peptide was incubated with increasing concentrations of either AAYSDQATPLLLSPR or AAYSDQATPLLGSPR peptide. After binding for 3 days at 37°C, the amount of biotinylated Ha peptide/HLA-DR1 complexes was measured with alkaline phosphatase-labeled streptavidin in an antibody-capture assay.
Figure 2.
Figure 2. Crystal Structure of HLA-DR1 Bound to AAYSDQATPLLLSPR(A) 2Fo-Fc electron density map contoured at 1σ using data in the resolution rage of 30–2.4 Å, with all peptide atoms omitted from the map calculation. The peptide carbon atoms are yellow, and nitrogen and oxygen atoms are blue and red, respectively.(B) The AAYSDQATPLLLSPR peptide from the HLA-DR1/SEC3-3B2 complex (carbon atoms colored in yellow) was superimposed with the peptides present in the structure of HLA-DR1 without the superantigen (carbon atoms colored in green or magenta for the two molecules in the asymmetric unit).(C) 2Fo-Fc electron density maps contoured at 1σ for the P10 region of HLA-DR1/AAYSDQATPLLLSPR. (All the labeled residues were omitted from the map calculation). The carbon atoms for the peptide are yellow, and the ones for HLA-DR1 are green. The view is from the right side of (A), with the α subunit helix to the right and the β subunit helix to the left.(D) Surface of the HLA-DR1 P10 region shown with the same view as (C). Residues lining the pocket are labeled. Residues β57 and β60 are polymorphic among HLA-DR proteins. Figures were generated with PyMol [43].
The above figures are reprinted by permission from Cell Press: Chem Biol (2004, 11, 1395-1402) copyright 2004.
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