7u21: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Human Class I MHC HLA-A2 in complex with AVGSYVYSV peptide== | |||
<StructureSection load='7u21' size='340' side='right'caption='[[7u21]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7u21]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7U21 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U21 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7u21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u21 OCA], [https://pdbe.org/7u21 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u21 RCSB], [https://www.ebi.ac.uk/pdbsum/7u21 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u21 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A140T913_HUMAN A0A140T913_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
There is long-standing interest in accurately modeling the structural features of peptides bound and presented by class I MHC proteins. This interest has grown with the advent of rapid genome sequencing and the prospect of personalized, peptide-based cancer vaccines, as well as the development of molecular and cellular therapeutics based on T cell receptor recognition of peptide-MHC. However, while the speed and accessibility of peptide-MHC modeling has improved substantially over the years, improvements in accuracy have been modest. Accuracy is crucial in peptide-MHC modeling, as T cell receptors are highly sensitive to peptide conformation and capturing fine details is therefore necessary for useful models. Studying nonameric peptides presented by the common class I MHC protein HLA-A*02:01, here we addressed a key question common to modern modeling efforts: from a set of models (or decoys) generated through conformational sampling, which is best? We found that the common strategy of decoy selection by lowest energy can lead to substantial errors in predicted structures. We therefore adopted a data-driven approach and trained functions capable of predicting near native decoys with exceptionally high accuracy. Although our implementation is limited to nonamer/HLA-A*02:01 complexes, our results serve as an important proof of concept from which improvements can be made and, given the significance of HLA-A*02:01 and its preference for nonameric peptides, should have immediate utility in select immunotherapeutic and other efforts for which structural information would be advantageous. | |||
Physicochemical Heuristics for Identifying High Fidelity, Near-Native Structural Models of Peptide/MHC Complexes.,Keller GLJ, Weiss LI, Baker BM Front Immunol. 2022 Apr 25;13:887759. doi: 10.3389/fimmu.2022.887759. eCollection , 2022. PMID:35547730<ref>PMID:35547730</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7u21" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
==See Also== | |||
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] | |||
*[[MHC 3D structures|MHC 3D structures]] | |||
*[[MHC I 3D structures|MHC I 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Baker BM]] | |||
[[Category: Weiss LI]] | |||
Latest revision as of 20:10, 18 October 2023
Human Class I MHC HLA-A2 in complex with AVGSYVYSV peptideHuman Class I MHC HLA-A2 in complex with AVGSYVYSV peptide
Structural highlights
FunctionPublication Abstract from PubMedThere is long-standing interest in accurately modeling the structural features of peptides bound and presented by class I MHC proteins. This interest has grown with the advent of rapid genome sequencing and the prospect of personalized, peptide-based cancer vaccines, as well as the development of molecular and cellular therapeutics based on T cell receptor recognition of peptide-MHC. However, while the speed and accessibility of peptide-MHC modeling has improved substantially over the years, improvements in accuracy have been modest. Accuracy is crucial in peptide-MHC modeling, as T cell receptors are highly sensitive to peptide conformation and capturing fine details is therefore necessary for useful models. Studying nonameric peptides presented by the common class I MHC protein HLA-A*02:01, here we addressed a key question common to modern modeling efforts: from a set of models (or decoys) generated through conformational sampling, which is best? We found that the common strategy of decoy selection by lowest energy can lead to substantial errors in predicted structures. We therefore adopted a data-driven approach and trained functions capable of predicting near native decoys with exceptionally high accuracy. Although our implementation is limited to nonamer/HLA-A*02:01 complexes, our results serve as an important proof of concept from which improvements can be made and, given the significance of HLA-A*02:01 and its preference for nonameric peptides, should have immediate utility in select immunotherapeutic and other efforts for which structural information would be advantageous. Physicochemical Heuristics for Identifying High Fidelity, Near-Native Structural Models of Peptide/MHC Complexes.,Keller GLJ, Weiss LI, Baker BM Front Immunol. 2022 Apr 25;13:887759. doi: 10.3389/fimmu.2022.887759. eCollection , 2022. PMID:35547730[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||