7mle - Revision history

OCA at 09:21, 25 October 2023

OCA — Wed, 25 Oct 2023 09:21:43 GMT

←Older revision		Revision as of 09:21, 25 October 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7mle]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Influenza_B_virus Influenza B virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MLE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MLE FirstGlance]. <br>		<table><tr><td colspan='2'>[[7mle]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Influenza_B_virus Influenza B virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MLE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MLE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7mle FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mle OCA], [https://pdbe.org/7mle PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mle RCSB], [https://www.ebi.ac.uk/pdbsum/7mle PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mle 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=7mle FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mle OCA], [https://pdbe.org/7mle PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mle RCSB], [https://www.ebi.ac.uk/pdbsum/7mle PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mle ProSAT]</span></td></tr>
	</table>		</table>

OCA at 09:37, 19 April 2023

OCA — Wed, 19 Apr 2023 09:37:41 GMT

←Older revision		Revision as of 09:37, 19 April 2023
Line 1:		Line 1:

-	====	+	==Crystal Structure of HLA-A*03:01 in complex with VVRPSVASK, an 9-mer epitope from Influenza B virus==
-	<StructureSection load='7mle' size='340' side='right'caption='[[7mle]]' scene=''>	+	<StructureSection load='7mle' size='340' side='right'caption='[[7mle]], [[Resolution\|resolution]] 2.20Å' 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'>[[7mle]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Influenza_B_virus Influenza B virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MLE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MLE 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=7mle FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mle OCA], [https://pdbe.org/7mle PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mle RCSB], [https://www.ebi.ac.uk/pdbsum/7mle PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mle 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=SO4:SULFATE+ION'>SO4</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=7mle FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mle OCA], [https://pdbe.org/7mle PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mle RCSB], [https://www.ebi.ac.uk/pdbsum/7mle PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mle ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/HLAA_HUMAN HLAA_HUMAN] Selection of immunotherapy in solid cancer;Birdshot chorioretinopathy;Prediction of phenytoin or carbamazepine toxicity. Alleles A02:01 and A24:02 are associated with increased susceptibility to diabetes mellitus, insulin-dependent (IDDM) (PubMed:22245737, PubMed:18802479, PubMed:16731854, PubMed:22522618). In a glucose-dependent way, allele A02:01 may aberrantly present the signal peptide of preproinsulin (ALWGPDPAAA) on the surface of pancreatic beta cells to autoreactive CD8-positive T cells, potentially driving T-cell mediated cytotoxicity in pancreatic islets (PubMed:22245737, PubMed:18802479). Allele A24:02 may present the signal peptide of preproinsulin (LWMRLLPLL) and contribute to acute pancreatic beta-cell destruction and early onset of IDDM (PubMed:16731854, PubMed:22522618).<ref>PMID:16731854</ref> <ref>PMID:18802479</ref> <ref>PMID:22245737</ref> <ref>PMID:22522618</ref> Allele A03:01 is associated with increased susceptibility to multiple sclerosis (MS), an autoimmune disease of the central nervous system (PubMed:10746785). May contribute to the initiation phase of the disease by presenting myelin PLP1 self-peptide (KLIETYFSK) to autoreactive CD8-positive T cells capable of initiating the first autoimmune attacks (PubMed:18953350).<ref>PMID:10746785</ref> <ref>PMID:18953350</ref> Allele A26:01 is associated with increased susceptibility to Behcet disease (BD) in the Northeast Asian population. Especially in the HLA-B51-negative BD populations, HLA-A26 is significantly associated with the onset of BD.<ref>PMID:30872678</ref> Allele A*29:02 is associated with increased susceptibility to birdshot chorioretinopathy (BSCR). May aberrantly present retinal autoantigens and induce autoimmune uveitis.<ref>PMID:1728143</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/HLAA_HUMAN HLAA_HUMAN] Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-A-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells (PubMed:2456340, PubMed:2784196, PubMed:1402688, PubMed:7504010, PubMed:9862734, PubMed:10449296, PubMed:12138174, PubMed:12393434, PubMed:15893615, PubMed:17189421, PubMed:19543285, PubMed:21498667, PubMed:24192765, PubMed:7694806, PubMed:24395804, PubMed:28250417). May also present self-peptides derived from the signal sequence of secreted or membrane proteins, although T cells specific for these peptides are usually inactivated to prevent autoreactivity (PubMed:25880248, PubMed:7506728, PubMed:7679507). Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells (PubMed:12796775, PubMed:18275829, PubMed:19542454, PubMed:28250417). Typically presents intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via IFNG-induced immunoproteasome or via endopeptidase IDE/insulin-degrading enzyme (PubMed:17189421, PubMed:20364150, PubMed:17079320, PubMed:26929325, PubMed:27049119). Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9 (PubMed:7504010, PubMed:9862734).<ref>PMID:10449296</ref> <ref>PMID:12138174</ref> <ref>PMID:12393434</ref> <ref>PMID:12796775</ref> <ref>PMID:1402688</ref> <ref>PMID:15893615</ref> <ref>PMID:17079320</ref> <ref>PMID:17189421</ref> <ref>PMID:18275829</ref> <ref>PMID:19542454</ref> <ref>PMID:19543285</ref> <ref>PMID:20364150</ref> <ref>PMID:21498667</ref> <ref>PMID:24192765</ref> <ref>PMID:24395804</ref> <ref>PMID:2456340</ref> <ref>PMID:25880248</ref> <ref>PMID:26929325</ref> <ref>PMID:27049119</ref> <ref>PMID:2784196</ref> <ref>PMID:28250417</ref> <ref>PMID:7504010</ref> <ref>PMID:7506728</ref> <ref>PMID:7679507</ref> <ref>PMID:7694806</ref> <ref>PMID:9862734</ref> Allele A01:01: Presents a restricted peptide repertoire including viral epitopes derived from IAV NP/nucleoprotein (CTELKLSDY), IAV PB1/polymerase basic protein 1 (VSDGGPNLY), HAdV-11 capsid L3/hexon protein (LTDLGQNLLY), SARS-CoV-2 3a/ORF3a (FTSDYYQLY) as well as tumor peptide antigens including MAGE1 (EADPTGHSY), MAGEA3 (EVDPIGHLY) and WT1 (TSEKRPFMCAY), all having in common a canonical motif with a negatively charged Asp or Glu residue at position 3 and a Tyr anchor residue at the C-terminus (PubMed:1402688, PubMed:7504010, PubMed:17189421, PubMed:20364150, PubMed:25880248, PubMed:30530481, PubMed:19177349, PubMed:24395804, PubMed:26758806, PubMed:32887977). A number of HLA-A01:01-restricted peptides carry a post-translational modification with oxidation and N-terminal acetylation being the most frequent (PubMed:25880248). Fails to present highly immunogenic peptides from the EBV latent antigens (PubMed:18779413).<ref>PMID:1402688</ref> <ref>PMID:17189421</ref> <ref>PMID:18779413</ref> <ref>PMID:19177349</ref> <ref>PMID:20364150</ref> <ref>PMID:24395804</ref> <ref>PMID:25880248</ref> <ref>PMID:26758806</ref> <ref>PMID:30530481</ref> <ref>PMID:7504010</ref> Allele A02:01: A major allele in human populations, presents immunodominant viral epitopes derived from IAV M/matrix protein 1 (GILGFVFTL), HIV-1 env (TLTSCNTSV), HIV-1 gag-pol (ILKEPVHGV), HTLV-1 Tax (LLFGYPVYV), HBV C/core antigen (FLPSDFFPS), HCMV UL83/pp65 (NLVPMVATV) as well as tumor peptide antigens including MAGEA4 (GVYDGREHTV), WT1 (RMFPNAPYL) and CTAG1A/NY-ESO-1 (SLLMWITQC), all having in common hydrophobic amino acids at position 2 and at the C-terminal anchors.<ref>PMID:11502003</ref> <ref>PMID:12138174</ref> <ref>PMID:12796775</ref> <ref>PMID:17079320</ref> <ref>PMID:18275829</ref> <ref>PMID:19542454</ref> <ref>PMID:20619457</ref> <ref>PMID:22245737</ref> <ref>PMID:26929325</ref> <ref>PMID:2784196</ref> <ref>PMID:28250417</ref> <ref>PMID:7694806</ref> <ref>PMID:7935798</ref> <ref>PMID:8630735</ref> <ref>PMID:8805302</ref> <ref>PMID:8906788</ref> <ref>PMID:9177355</ref> Allele A03:01: Presents viral epitopes derived from IAV NP (ILRGSVAHK), HIV-1 nef (QVPLRPMTYK), HIV-1 gag-pol (AIFQSSMTK), SARS-CoV-2 N/nucleoprotein (KTFPPTEPK) as well as tumor peptide antigens including PMEL (LIYRRRLMK), NODAL (HAYIQSLLK), TRP-2 (RMYNMVPFF), all having in common hydrophobic amino acids at position 2 and Lys or Arg anchor residues at the C-terminus (PubMed:7504010, PubMed:7679507, PubMed:9862734, PubMed:19543285, PubMed:21943705, PubMed:2456340, PubMed:32887977). May also display spliced peptides resulting from the ligation of two separate proteasomal cleavage products that are not contiguous in the parental protein (PubMed:27049119).<ref>PMID:19543285</ref> <ref>PMID:21943705</ref> <ref>PMID:2456340</ref> <ref>PMID:27049119</ref> <ref>PMID:7504010</ref> <ref>PMID:7679507</ref> <ref>PMID:9862734</ref> Allele A11:01: Presents several immunodominant epitopes derived from HIV-1 gag-pol and HHV-4 EBNA4, containing the peptide motif with Val, Ile, Thr, Leu, Tyr or Phe at position 2 and Lys anchor residue at the C-terminus. Important in the control of HIV-1, EBV and HBV infections (PubMed:10449296). Presents an immunodominant epitope derived from SARS-CoV-2 N/nucleoprotein (KTFPPTEPK) (PubMed:32887977).<ref>PMID:10449296</ref> <ref>PMID:32887977</ref> Allele A23:01: Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response.<ref>PMID:17182537</ref> Allele A24:02: Presents viral epitopes derived from HIV-1 nef (RYPLTFGWCF), EBV lytic- and latent-cycle antigens BRLF1 (TYPVLEEMF), BMLF1 (DYNFVKQLF) and LMP2 (IYVLVMLVL), SARS-CoV nucleocapsid/N (QFKDNVILL), as well as tumor peptide antigens including PRAME (LYVDSLFFL), all sharing a common signature motif, namely an aromatic residue Tyr or Phe at position 2 and a nonhydrophobic anchor residue Phe, Leu or Iso at the C-terminus (PubMed:9047241, PubMed:12393434, PubMed:24192765, PubMed:20844028). Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response (PubMed:17182537, PubMed:18502829).<ref>PMID:12393434</ref> <ref>PMID:17182537</ref> <ref>PMID:18502829</ref> <ref>PMID:20844028</ref> <ref>PMID:24192765</ref> <ref>PMID:9047241</ref> Allele A26:01: Presents several epitopes derived from HIV-1 gag-pol (EVIPMFSAL, ETKLGKAGY) and env (LVSDGGPNLY), carrying as anchor residues preferentially Glu at position 1, Val or Thr at position 2 and Tyr at the C-terminus.<ref>PMID:15893615</ref> Allele A29:02: Presents peptides having a common motif, namely a Glu residue at position 2 and Tyr or Leu anchor residues at the C-terminus.<ref>PMID:8622959</ref> Allele A32:01: Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response.<ref>PMID:17182537</ref> Allele A68:01: Presents viral epitopes derived from IAV NP (KTGGPIYKR) and HIV-1 tat (ITKGLGISYGR), having a common signature motif namely, Val or Thr at position 2 and positively charged residues Arg or Lys at the C-terminal anchor.<ref>PMID:1448153</ref> <ref>PMID:1448154</ref> <ref>PMID:2784196</ref> Allele A74:01: Presents immunodominant HIV-1 epitopes derived from gag-pol (GQMVHQAISPR, QIYPGIKVR) and rev (RQIHSISER), carrying an aliphatic residue at position 2 and Arg anchor residue at the C-terminus. May contribute to viral load control in chronic HIV-1 infection.<ref>PMID:21498667</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	OBJECTIVE: Influenza A, B and C viruses (IAV, IBV and ICV, respectively) circulate globally, infecting humans and causing widespread morbidity and mortality. Here, we investigate the T cell response towards an immunodominant IAV epitope, NP(265-273,) and its IBV and ICV homologues, presented by HLA-A03:01 molecule expressed in ~ 4% of the global population (~ 300 million people). METHODS: We assessed the magnitude (tetramer staining) and quality of the CD8(+) T cell response (intracellular cytokine staining) towards NP(265-IAV) and described the T cell receptor (TCR) repertoire used to recognise this immunodominant epitope. We next assessed the immunogenicity of NP(265-IAV) homologue peptides from IBV and ICV and the ability of CD8(+) T cells to cross-react towards these homologous peptides. Furthermore, we determined the structures of NP(265-IAV) and NP(323-IBV) peptides in complex with HLA-A03:01 by X-ray crystallography. RESULTS: Our study provides a detailed characterisation of the CD8(+) T cell response towards NP(265-IAV) and its IBV and ICV homologues. The data revealed a diverse repertoire for NP(265-IAV) that is associated with superior anti-viral protection. Evidence of cross-reactivity between the three different influenza virus strain-derived epitopes was observed, indicating the discovery of a potential vaccination target that is broad enough to cover all three influenza strains. CONCLUSION: We show that while there is a potential to cross-protect against distinct influenza virus lineages, the T cell response was stronger against the IAV peptide than IBV or ICV, which is an important consideration when choosing targets for future vaccine design.
		+
		+	Homologous peptides derived from influenza A, B and C viruses induce variable CD8(+) T cell responses with cross-reactive potential.,Nguyen AT, Lau HMP, Sloane H, Jayasinghe D, Mifsud NA, Chatzileontiadou DS, Grant EJ, Szeto C, Gras S Clin Transl Immunology. 2022 Oct 19;11(10):e1422. doi: 10.1002/cti2.1422. , eCollection 2022. PMID:36275878<ref>PMID:36275878</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7mle" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta-2 microglobulin 3D structures\|Beta-2 microglobulin 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Influenza B virus]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Gras S]]
		+	[[Category: Nguyen AT]]
		+	[[Category: Szeto C]]

OCA at 10:23, 6 April 2022

OCA — Wed, 06 Apr 2022 10:23:30 GMT

←Older revision		Revision as of 10:23, 6 April 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

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

OCA at 08:10, 12 May 2021

OCA — Wed, 12 May 2021 08:10:13 GMT

←Older revision		Revision as of 08:10, 12 May 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 05 May 2021 07:27:55 GMT

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

←Older revision

Revision as of 07:27, 5 May 2021

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

OCA — Wed, 05 May 2021 07:27:54 GMT

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

New page

'''Unreleased structure'''

The entry 7mle is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]