8esh: Difference between revisions

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~~'''Unreleased structure'''~~

~~The entry~~ 8esh is ~~ON HOLD until Paper~~ Publication

==Structure of chimeric HLA-A*02:01 bound to CMV peptide==

== Structural highlights ==

<table><tr><td colspan='2'>[[8esh]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_betaherpesvirus_5 Human betaherpesvirus 5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ESH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ESH 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]] 2.72Å</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=8esh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8esh OCA], [https://pdbe.org/8esh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8esh RCSB], [https://www.ebi.ac.uk/pdbsum/8esh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8esh ProSAT]</span></td></tr>

</table>

== Function ==

[https://www.uniprot.org/uniprot/D2KZ37_HUMAN D2KZ37_HUMAN]

== Publication Abstract from PubMed ==

Major Histocompatibility Complex class I (MHC-I) molecules display self, viral or aberrant epitopic peptides to T cell receptors (TCRs), which employ interactions between complementarity-determining regions with both peptide and MHC-I heavy chain 'framework' residues to recognize specific Human Leucocyte Antigens (HLAs). The highly polymorphic nature of the HLA peptide-binding groove suggests a malleability of interactions within a common structural scaffold. Here, using structural data from peptide:MHC-I and pMHC:TCR structures, we first identify residues important for peptide and/or TCR binding. We then outline a fixed-backbone computational design approach for engineering synthetic molecules that combine peptide binding and TCR recognition surfaces from existing HLA allotypes. X-ray crystallography demonstrates that chimeric molecules bridging divergent HLA alleles can bind selected peptide antigens in a specified backbone conformation. Finally, in vitro tetramer staining and biophysical binding experiments using chimeric pMHC-I molecules presenting established antigens further demonstrate the requirement of TCR recognition on interactions with HLA framework residues, as opposed to interactions with peptide-centric Chimeric Antigen Receptors (CARs). Our results underscore a novel, structure-guided platform for developing synthetic HLA molecules with desired properties as screening probes for peptide-centric interactions with TCRs and other therapeutic modalities.

~~Authors~~:

Decoupling peptide binding from T cell receptor recognition with engineered chimeric MHC-I molecules.,Papadaki GF, Ani O, Florio TJ, Young MC, Danon JN, Sun Y, Dersh D, Sgourakis NG Front Immunol. 2023 Jan 25;14:1116906. doi: 10.3389/fimmu.2023.1116906. , eCollection 2023. PMID:36761745<ref>PMID:36761745</ref>

~~Description~~:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased~~ Structures]]

</div>

==See Also==

*[[MHC 3D structures|MHC 3D structures]]

*[[MHC I 3D structures|MHC I 3D structures]]

== References ==

__TOC__

</StructureSection>

[[Category: Homo sapiens]]

[[Category: Human betaherpesvirus 5]]

[[Category: Large Structures]]

[[Category: Ani O]]

[[Category: Florio TJ]]

[[Category: Mallik L]]

[[Category: Sgourakis NG]]

[[Category: Young MC]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8esh is ON HOLD  until Paper Publication
+==Structure of chimeric HLA-A*02:01 bound to CMV peptide==
+<StructureSection load='8esh' size='340' side='right'caption='[[8esh]], [[Resolution|resolution]] 2.72&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8esh]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_betaherpesvirus_5 Human betaherpesvirus 5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ESH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ESH 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]] 2.72&#8491;</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=8esh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8esh OCA], [https://pdbe.org/8esh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8esh RCSB], [https://www.ebi.ac.uk/pdbsum/8esh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8esh ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/D2KZ37_HUMAN D2KZ37_HUMAN]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Major Histocompatibility Complex class I (MHC-I) molecules display self, viral or aberrant epitopic peptides to T cell receptors (TCRs), which employ interactions between complementarity-determining regions with both peptide and MHC-I heavy chain 'framework' residues to recognize specific Human Leucocyte Antigens (HLAs). The highly polymorphic nature of the HLA peptide-binding groove suggests a malleability of interactions within a common structural scaffold. Here, using structural data from peptide:MHC-I and pMHC:TCR structures, we first identify residues important for peptide and/or TCR binding. We then outline a fixed-backbone computational design approach for engineering synthetic molecules that combine peptide binding and TCR recognition surfaces from existing HLA allotypes. X-ray crystallography demonstrates that chimeric molecules bridging divergent HLA alleles can bind selected peptide antigens in a specified backbone conformation. Finally, in vitro tetramer staining and biophysical binding experiments using chimeric pMHC-I molecules presenting established antigens further demonstrate the requirement of TCR recognition on interactions with HLA framework residues, as opposed to interactions with peptide-centric Chimeric Antigen Receptors (CARs). Our results underscore a novel, structure-guided platform for developing synthetic HLA molecules with desired properties as screening probes for peptide-centric interactions with TCRs and other therapeutic modalities.
-Authors:
+Decoupling peptide binding from T cell receptor recognition with engineered chimeric MHC-I molecules.,Papadaki GF, Ani O, Florio TJ, Young MC, Danon JN, Sun Y, Dersh D, Sgourakis NG Front Immunol. 2023 Jan 25;14:1116906. doi: 10.3389/fimmu.2023.1116906. , eCollection 2023. PMID:36761745<ref>PMID:36761745</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8esh" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[MHC 3D structures|MHC 3D structures]]
+*[[MHC I 3D structures|MHC I 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Human betaherpesvirus 5]]
+[[Category: Large Structures]]
+[[Category: Ani O]]
+[[Category: Florio TJ]]
+[[Category: Mallik L]]
+[[Category: Sgourakis NG]]
+[[Category: Young MC]]