7pbc - Revision history

OCA at 13:03, 1 February 2024

2024-02-01T13:03:32Z

←Older revision		Revision as of 13:03, 1 February 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7pbc]] 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=7PBC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PBC FirstGlance]. <br>		<table><tr><td colspan='2'>[[7pbc]] 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=7PBC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PBC FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <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]] 2.04Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <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=7pbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pbc OCA], [https://pdbe.org/7pbc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pbc RCSB], [https://www.ebi.ac.uk/pdbsum/7pbc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pbc 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=7pbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pbc OCA], [https://pdbe.org/7pbc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pbc RCSB], [https://www.ebi.ac.uk/pdbsum/7pbc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pbc ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/MAGAA_HUMAN MAGAA_HUMAN]] Not known, though may play a role in embryonal development and tumor transformation or aspects of tumor progression.	+	[https://www.uniprot.org/uniprot/MAGAA_HUMAN MAGAA_HUMAN] Not known, though may play a role in embryonal development and tumor transformation or aspects of tumor progression.
	<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 7pbc" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7pbc" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta-2 microglobulin 3D structures\|Beta-2 microglobulin 3D structures]]
		+	*[[T-cell receptor 3D structures\|T-cell receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 03:08, 8 September 2022

2022-09-08T03:08:29Z

←Older revision		Revision as of 03:08, 8 September 2022
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-	====	+	==Crystal structure of engineered TCR (796) complexed to HLA-A*02:01 presenting MAGE-A10 9-mer peptide==
-	<StructureSection load='7pbc' size='340' side='right'caption='[[7pbc]]' scene=''>	+	<StructureSection load='7pbc' size='340' side='right'caption='[[7pbc]], [[Resolution\|resolution]] 2.04Å' 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'>[[7pbc]] 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=7PBC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PBC 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=7pbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pbc OCA], [https://pdbe.org/7pbc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pbc RCSB], [https://www.ebi.ac.uk/pdbsum/7pbc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pbc 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=CL:CHLORIDE+ION'>CL</scene>, <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=7pbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pbc OCA], [https://pdbe.org/7pbc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pbc RCSB], [https://www.ebi.ac.uk/pdbsum/7pbc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pbc ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/MAGAA_HUMAN MAGAA_HUMAN]] Not known, though may play a role in embryonal development and tumor transformation or aspects of tumor progression.
		+	<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 7pbc" 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 04:50, 3 August 2022

2022-08-03T04:50:57Z

←Older revision		Revision as of 04:50, 3 August 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7pbc ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7pbc' size='340' side='right'caption='[[7pbc]]' 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=7pbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pbc OCA], [https://pdbe.org/7pbc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pbc RCSB], [https://www.ebi.ac.uk/pdbsum/7pbc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pbc ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 07:28, 8 September 2021

2021-09-08T07:28:15Z

←Older revision		Revision as of 07:28, 8 September 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7pbc is ON HOLD	+	The entry 7pbc is ON HOLD until Paper Publication

	Authors:		Authors:

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

2021-08-11T05:04:36Z

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

←Older revision

Revision as of 05:04, 11 August 2021

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

2021-08-11T05:04:35Z

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

New page

'''Unreleased structure'''

The entry 7pbc is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]