7qpj - Revision history

OCA at 13:20, 1 February 2024

OCA — Thu, 01 Feb 2024 13:20:50 GMT

←Older revision		Revision as of 13:20, 1 February 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7qpj]] is a 5 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=7QPJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QPJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[7qpj]] is a 5 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=7QPJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QPJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.54Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=7qpj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qpj OCA], [https://pdbe.org/7qpj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qpj RCSB], [https://www.ebi.ac.uk/pdbsum/7qpj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qpj ProSAT]</span></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=7qpj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qpj OCA], [https://pdbe.org/7qpj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qpj RCSB], [https://www.ebi.ac.uk/pdbsum/7qpj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qpj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/Q861F7_HUMAN Q861F7_HUMAN]]	+	[https://www.uniprot.org/uniprot/Q861F7_HUMAN Q861F7_HUMAN]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 7qpj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7qpj" style="background-color:#fffaf0;"></div>
		+
		+	==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]]
		+	*[[T-cell receptor 3D structures\|T-cell receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 03:11, 8 September 2022

OCA — Thu, 08 Sep 2022 03:11:59 GMT

←Older revision		Revision as of 03:11, 8 September 2022
Line 1:		Line 1:

-	====	+	==Crystal structure of engineered TCR (756) complexed to HLA-A*02:01 presenting MAGE-A10 9-mer peptide==
-	<StructureSection load='7qpj' size='340' side='right'caption='[[7qpj]]' scene=''>	+	<StructureSection load='7qpj' size='340' side='right'caption='[[7qpj]], [[Resolution\|resolution]] 1.54Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7qpj]] is a 5 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=7QPJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QPJ FirstGlance]. <br>
-	</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=7qpj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qpj OCA], [https://pdbe.org/7qpj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qpj RCSB], [https://www.ebi.ac.uk/pdbsum/7qpj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qpj ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=7qpj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qpj OCA], [https://pdbe.org/7qpj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qpj RCSB], [https://www.ebi.ac.uk/pdbsum/7qpj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qpj ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/Q861F7_HUMAN Q861F7_HUMAN]]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BACKGROUND: T-cell receptor (TCR) immunotherapy is becoming a viable modality in cancer treatment with efficacy in clinical trials. The safety of patients is paramount, so innovative cell engineering methods are being employed to exploit adaptive immunity while controlling the factors governing antigen receptor (ie, TCR) specificity and cross-reactivity. We recently reported a TCR engineering campaign and selectivity profiling assay (X-scan) targeting a melanoma antigen gene (MAGE)-A10 peptide. This helped to distinguish between two well-performing TCRs based on cross-reactivity potential during preclinical drug evaluation, allowing one to be advanced to T-cell immunotherapeutic clinical trials. Here, we present three-dimensional structural information on those TCRs, highlighting engineering improvements and molecular mechanisms likely underpinning differential selectivity. METHODS: Parental and engineered TCRs were purified and crystallized either alone or complexed to human leucocyte antigen (HLA)-A*02:01 presenting the MAGE-A10 9-mer peptide, GLYDGMEHL (pHLA/MAGE-A10-9). Using X-ray diffraction, we solved four high-resolution crystal structures and evaluated them relative to previously reported functional results. RESULTS: The unligated parental TCR displayed similar complementarity-determining region (CDR) loop conformations when bound to pHLA/MAGE-A10-9; a rigid-body movement of TCR beta chain variable domain (TRBV) relative to TCR alpha chain variable domain helped optimal pHLA engagement. This first view of an HLA-bound MAGE-A10 peptide revealed an intrachain non-covalent 'staple' between peptide Tyr3 and Glu7. A subtle Glu53-Asp mutation in betaCDR2 of the parental TCR generated a high-affinity derivative. Its pHLA-complexed structure shows that the shorter Asp leans toward the pHLA with resulting rigid-body TRBV shift, creating localized changes around the peptide's C-terminus. Structural comparison with a less selective TCR indicated that differential cross-reactivity to MAGE-A10 peptide variants is most readily explained by alterations in surface electrostatics, and the size and geometry of TCR-peptide interfacial cavities. CONCLUSIONS: Modest changes in engineered TCRs targeting MAGE-A10 produced significantly different properties. Conformational invariance of TCR and antigen peptide plus more space-filling CDR loop sequences may be desirable properties for clinically relevant TCR-pHLA systems to reduce the likelihood of structurally similar peptide mimics being tolerated by a TCR. Such properties may partially explain why the affinity-enhanced, in vitro-selected TCR has been generally well tolerated in patients.
		+
		+	Structural insights into engineering a T-cell receptor targeting MAGE-A10 with higher affinity and specificity for cancer immunotherapy.,Simister PC, Border EC, Vieira JF, Pumphrey NJ J Immunother Cancer. 2022 Jul;10(7). pii: jitc-2022-004600. doi:, 10.1136/jitc-2022-004600. PMID:35851311<ref>PMID:35851311</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7qpj" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Border EC]]
		+	[[Category: Pumphrey NJ]]
		+	[[Category: Simister PC]]
		+	[[Category: Vieira JF]]

OCA at 04:51, 3 August 2022

OCA — Wed, 03 Aug 2022 04:51:50 GMT

←Older revision		Revision as of 04:51, 3 August 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7qpj ~~is ON HOLD~~	+	====
-		+	<StructureSection load='7qpj' size='340' side='right'caption='[[7qpj]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~:	+	</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=7qpj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qpj OCA], [https://pdbe.org/7qpj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qpj RCSB], [https://www.ebi.ac.uk/pdbsum/7qpj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qpj ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA: Protected "7qpj" [edit=sysop:move=sysop]

OCA — Wed, 12 Jan 2022 08:31:23 GMT

Protected "7qpj" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:31, 12 January 2022

OCA: New page: '''Unreleased structure''' The entry 7qpj is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 12 Jan 2022 08:31:22 GMT

New page: '''Unreleased structure''' The entry 7qpj is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7qpj is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]