5vz5 - Revision history

OCA at 14:03, 4 October 2023

2023-10-04T14:03:11Z

←Older revision		Revision as of 14:03, 4 October 2023
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	<StructureSection load='5vz5' size='340' side='right'caption='[[5vz5]], [[Resolution\|resolution]] 2.59Å' scene=''>		<StructureSection load='5vz5' size='340' side='right'caption='[[5vz5]], [[Resolution\|resolution]] 2.59Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vz5]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VZ5 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5VZ5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vz5]] is a 3 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=5VZ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VZ5 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>~~, ~~<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]] 2.5901Å</td></tr>
-	<tr id='~~activity~~'><td class="sblockLbl"><b>~~Activity~~:</b></td><td class="sblockDat"><~~span class~~='~~plainlinks~~'>~~[http:~~/~~/en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase]~~, ~~with EC number [http~~:~~//www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1]~~ </~~span~~></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>, <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'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5vz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vz5 OCA], [~~http~~://pdbe.org/5vz5 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5vz5 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5vz5 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5vz5 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=5vz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vz5 OCA], [https://pdbe.org/5vz5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vz5 RCSB], [https://www.ebi.ac.uk/pdbsum/5vz5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vz5 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/~~1B15_HUMAN 1B15_HUMAN~~]~~] Defects in HLA~~-~~B are a cause~~ of susceptibility to Stevens-Johnson syndrome ~~(SJS) [MIM~~:~~[http~~:/~~/omim.org/~~entry~~/608579 608579]]~~. A ~~rare blistering mucocutaneous disease that share clinical and histopathologic features~~ with ~~toxic epidermal necrolysis. Both disorders are characterized by high fever, malaise,~~ and ~~a rapidly developing blistering exanthema of macules and target~~-~~like lesions accompanied by mucosal involvement. Stevens-Johnson syndrome is a milder disease characterized by destruction~~ and ~~detachment~~ of the skin epithelium and mucous membranes involving less than 10% of the body surface area. Ocular symptoms include ulcerative conjunctivitis, keratitis, iritis, uveitis and sometimes blindness. It can be caused by a severe adverse reaction to particular types of medication, although Mycoplasma infections may induce some cases. Note=Allele B*15:02 is ~~associated with susceptibility to Stevens-Johnson syndrome~~. ~~[[http~~:~~//www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects~~ in ~~B2M are~~ the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:~~16549777~~</ref> ~~Note=Beta~~-~~2-microglobulin may adopt the fibrillar configuration of amyloid in~~ certain ~~pathologic states~~. The ~~capacity~~ to ~~assemble into amyloid fibrils is concentration dependent. Persistently high beta~~(2)-~~microglobulin serum levels lead~~ to ~~amyloidosis~~ in ~~patients on long~~-~~term hemodialysis~~.<ref>PMID:~~3532124~~</ref> ~~<ref>PMID~~:~~1336137</ref> <ref>PMID~~:~~7554280</ref> <ref>PMID~~:~~4586824<~~/~~ref> <ref>PMID:8084451<~~/~~ref> <ref>PMID:12119416<~~/~~ref> <ref>PMID:12796775<~~/~~ref>~~ <ref>PMID:~~16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224~~</ref> <ref>PMID:~~19284997~~</ref>	+	[https://www.uniprot.org/uniprot/HLAB_HUMAN HLAB_HUMAN] Prediction of allopurinol toxicity;NON RARE IN EUROPE: Ankylosing spondylitis;Prediction of flucloxacilline toxicity;Giant cell arteritis;Takayasu arteritis;Reactive arthritis;Behcet disease;Stevens-Johnson syndrome;Prediction of phenytoin or carbamazepine toxicity;Pulmonary arterial hypertension associated with connective tissue disease;Prediction of abacavir toxicity. Disease susceptibility is associated with variants affecting the gene represented in this entry. Increased susceptibility to Stevens-Johnson syndrome is conferred by allele B15:02.<ref>PMID:15057820</ref> Disease susceptibility is associated with variants affecting the gene represented in this entry. A restricted number of HLA-B27 subtypes can be associated with ankylosing spondylitis and other B27-related diseases, and an elevated frequency of the B27:02 allele in ankylosing spondylitis patients is identified. The allele B27:07 seems to have a protective role in some populations because it was found only in the healthy controls.<ref>PMID:15603872</ref> There is evidence that HLA-B51 is associated with susceptibility to Behcet disease (BD). However, it is not certain whether HLA-B51 itself or a closely linked gene is responsible for susceptibility. The world distribution of HLA-B51 in healthy people corresponds to the global distribution of BD; in Southern hemisphere countries (Africa, South Pacific, etc.) and in some parts of Europe, the prevalence of HLA-B51 in healthy people is low or null, corresponding to a low prevalence of BD. The wide variation that exists in the relative risk of HLA-B51 would support other nongenetic risk factors.<ref>PMID:23291587</ref> The presence of allele B57:01 is associated with increased susceptibility to abacavir hypersensitivity [MIM:[https://omim.org/entry/142830 142830] in HIV-1 patients.<ref>PMID:11888582</ref> Allele group B08 is associated with increased susceptibility to rheumatoid arthritis, where affected individuals have antibodies to cyclic citrullinated peptide (anti-CCP-positive rheumatoid arthritis).<ref>PMID:22286218</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~1B15_HUMAN 1B15_HUMAN~~]~~] Involved in~~ the ~~presentation~~ of ~~foreign~~ antigens to the ~~immune system~~. ~~[[http~~://~~www~~.~~uniprot~~.~~org~~/~~uniprot~~/~~B2MG_HUMAN B2MG_HUMAN]] Component~~ of the ~~class I major histocompatibility~~ complex (~~MHC~~). ~~Involved~~ in the ~~presentation~~ of peptide ~~antigens~~ to the ~~immune system~~.	+	[https://www.uniprot.org/uniprot/HLAB_HUMAN HLAB_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-B-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells (PubMed:25808313, PubMed:29531227, PubMed:9620674, PubMed:23209413). 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:7743181, PubMed:18991276). 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:29531227, PubMed:9620674, PubMed:24600035). Typically presents intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via constitutive proteasome and IFNG-induced immunoproteasome (PubMed:23209413). Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9 (PubMed:25808313, PubMed:29531227).<ref>PMID:18991276</ref> <ref>PMID:23209413</ref> <ref>PMID:24600035</ref> <ref>PMID:25808313</ref> <ref>PMID:29531227</ref> <ref>PMID:7743181</ref> <ref>PMID:9620674</ref> Allele B07:02: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and mainly a Leu anchor residue at the C-terminus (PubMed:7743181). Presents a long peptide (APRGPHGGAASGL) derived from the cancer-testis antigen CTAG1A/NY-ESO-1, eliciting a polyclonal CD8-positive T cell response against tumor cells (PubMed:29531227). Presents viral epitopes derived from HIV-1 gag-pol (TPQDLNTML) and Nef (RPQVPLRPM) (PubMed:25808313). Presents an immunodominant epitope derived from SARS-CoV-2 N/nucleoprotein (SPRWYFYYL) (PubMed:32887977). Displays self-peptides including a peptide derived from the signal sequence of HLA-DPB1 (APRTVALTA) (PubMed:7743181).<ref>PMID:25808313</ref> <ref>PMID:29531227</ref> <ref>PMID:32887977</ref> <ref>PMID:7743181</ref> Allele B08:01: Presents to CD8-positive T cells viral epitopes derived from EBV/HHV-4 EBNA3 (QAKWRLQTL), eliciting cytotoxic T cell response.<ref>PMID:9620674</ref> Allele B13:02: Presents multiple HIV-1 epitopes derived from gag (RQANFLGKI, GQMREPRGSDI), nef (RQDILDLWI), gag-pol (RQYDQILIE, GQGQWTYQI) and rev (LQLPPLERL), all having in common a Gln residue at position 2 and mainly hydrophobic amino acids Leu, Ile or Val at the C-terminus. Associated with succesful control of HIV-1 infection.<ref>PMID:17251285</ref> Allele B18:01: Preferentially presents octomeric and nonameric peptides sharing a common motif, namely a Glu at position 2 and Phe or Tyr anchor residues at the C-terminus (PubMed:14978097, PubMed:23749632, PubMed:18991276). Presents an EBV/HHV-4 epitope derived from BZLF1 (SELEIKRY) (PubMed:23749632). May present to CD8-positive T cells an antigenic peptide derived from MAGEA3 (MEVDPIGHLY), triggering an anti-tumor immune response (PubMed:12366779). May display a broad repertoire of self-peptides with a preference for peptides derived from RNA-binding proteins (PubMed:14978097).<ref>PMID:12366779</ref> <ref>PMID:14978097</ref> <ref>PMID:18991276</ref> <ref>PMID:23749632</ref> Allele B27:05: Presents to CD8-positive T cells immunodominant viral epitopes derived from HCV POLG (ARMILMTHF), HIV-1 gag (KRWIILGLNK), IAV NP (SRYWAIRTR), SARS-CoV-2 N/nucleoprotein (QRNAPRITF), EBV/HHV-4 EBNA4 (HRCQAIRKK) and EBV/HHV-4 EBNA6 (RRIYDLIEL), confering longterm protection against viral infection (PubMed:19139562, PubMed:18385228, PubMed:15113903, PubMed:9620674, PubMed:32887977). Can present self-peptides derived from cytosolic and nuclear proteins. All peptides carry an Arg at position 2 (PubMed:1922338). The peptide-bound form interacts with NK cell inhibitory receptor KIR3DL1 and inhibits NK cell activation in a peptide-specific way, being particularly sensitive to the nature of the amino acid side chain at position 8 of the antigenic peptide (PubMed:8879234, PubMed:15657948). KIR3DL1 fails to recognize HLA-B27:05 in complex with B2M and EBV/HHV-4 EBNA6 (RRIYDLIEL) peptide, which can lead to increased activation of NK cells during infection (PubMed:15657948). May present an altered repertoire of peptides in the absence of TAP1-TAP2 and TAPBPL (PubMed:9620674).<ref>PMID:15113903</ref> <ref>PMID:15657948</ref> <ref>PMID:18385228</ref> <ref>PMID:19139562</ref> <ref>PMID:1922338</ref> <ref>PMID:8879234</ref> <ref>PMID:9620674</ref> Allele B40:01: Presents immunodominant viral epitopes derived from EBV/HHV-4 LMP2 (IEDPPFNSL) and SARS-CoV-2 N/nucleoprotein (MEVTPSGTWL), triggering memory CD8-positive T cell response (PubMed:18991276, PubMed:32887977). Displays self-peptides sharing a signature motif, namely a Glu at position 2 and a Leu anchor residue at the C-terminus (PubMed:18991276).<ref>PMID:18991276</ref> <ref>PMID:32887977</ref> Allele B41:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B44:02: Presents immunodominant viral epitopes derived from EBV/HHV-4 EBNA4 (VEITPYKPTW) and EBNA6 (AEGGVGWRHW, EENLLDFVRF), triggering memory CD8-positive T cell response (PubMed:9620674, PubMed:18991276). Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Phe, Tyr or Trp anchor residues at the C-terminus (PubMed:18991276).<ref>PMID:18991276</ref> <ref>PMID:9620674</ref> Allele B45:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B46:01: Preferentially presents nonameric peptides sharing a signature motif, namely Ala and Leu at position 2 and Tyr, Phe, Leu, or Met anchor residues at the C-terminus. The peptide-bound form interacts with KIR2DL3 and inhibits NK cell cytotoxic response in a peptide-specific way.<ref>PMID:28514659</ref> Allele B47:01: Displays self-peptides sharing a signature motif, namely an Asp at position 2 and Leu or Met anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B49:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ile or Val anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B50:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B51:01: Presents an octomeric HIV-1 epitope derived from gag-pol (TAFTIPSI) to the public TRAV17/TRBV7-3 TCR clonotype, strongly suppressing HIV-1 replication.<ref>PMID:24600035</ref> Allele B54:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.<ref>PMID:7743181</ref> Allele B55:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.<ref>PMID:7743181</ref> Allele B56:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.<ref>PMID:7743181</ref> Allele B57:01: The peptide-bound form recognizes KIR3DL1 and inhibits NK cell cytotoxic response.<ref>PMID:22020283</ref> <ref>PMID:25480565</ref> Allele B67:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Leu anchor residue at the C-terminus.<ref>PMID:7743181</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Receptor protein-tyrosine kinase]]~~	+	[[Category: Haussler D]]
-	[[Category: Haussler, D]]	+	[[Category: Rao AA]]
-	[[Category: Rao~~, A A~~]]	+	[[Category: Salama S]]
-	[[Category: Salama, S]]	+	[[Category: Sgourakis NG]]
-	[[Category: Sgourakis~~, N G~~]]	+	[[Category: Toor J]]
-	[[Category: Toor, J]]	+	[[Category: Tripathi S]]
-	[[Category: Tripathi, S]]	+
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Human major histocompatibility complex class i]]~~	+
-	~~[[Category: Immune system]]~~	+
-	~~[[Category: Lymphoma kinase-derived neuroblastoma tumor antigen]]~~	+
-	~~[[Category: Mhc-i~~]]	+

OCA at 08:45, 30 September 2020

2020-09-30T08:45:44Z

←Older revision		Revision as of 08:45, 30 September 2020
Line 1:		Line 1:

	==Crystal structure of an anaplastic lymphoma kinase-derived neuroblastoma tumor antigen bound to the Human Major Histocompatibility Complex Class I molecule HLA-B*1501==		==Crystal structure of an anaplastic lymphoma kinase-derived neuroblastoma tumor antigen bound to the Human Major Histocompatibility Complex Class I molecule HLA-B*1501==
-	<StructureSection load='5vz5' size='340' side='right' caption='[[5vz5]], [[Resolution\|resolution]] 2.59Å' scene=''>	+	<StructureSection load='5vz5' size='340' side='right'caption='[[5vz5]], [[Resolution\|resolution]] 2.59Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vz5]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VZ5 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5VZ5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vz5]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VZ5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5VZ5 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5vz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vz5 OCA], [http://pdbe.org/5vz5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vz5 RCSB], [http://www.ebi.ac.uk/pdbsum/5vz5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vz5 ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5vz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vz5 OCA], [http://pdbe.org/5vz5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vz5 RCSB], [http://www.ebi.ac.uk/pdbsum/5vz5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vz5 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5vz5" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5vz5" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta-2 microglobulin 3D structures\|Beta-2 microglobulin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Haussler, D]]		[[Category: Haussler, D]]

OCA at 07:33, 21 March 2018

2018-03-21T07:33:05Z

←Older revision		Revision as of 07:33, 21 March 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5vz5 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of an anaplastic lymphoma kinase-derived neuroblastoma tumor antigen bound to the Human Major Histocompatibility Complex Class I molecule HLA-B*1501==
		+	<StructureSection load='5vz5' size='340' side='right' caption='[[5vz5]], [[Resolution\|resolution]] 2.59Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5vz5]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VZ5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VZ5 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5vz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vz5 OCA], [http://pdbe.org/5vz5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vz5 RCSB], [http://www.ebi.ac.uk/pdbsum/5vz5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vz5 ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/1B15_HUMAN 1B15_HUMAN]] Defects in HLA-B are a cause of susceptibility to Stevens-Johnson syndrome (SJS) [MIM:[http://omim.org/entry/608579 608579]]. A rare blistering mucocutaneous disease that share clinical and histopathologic features with toxic epidermal necrolysis. Both disorders are characterized by high fever, malaise, and a rapidly developing blistering exanthema of macules and target-like lesions accompanied by mucosal involvement. Stevens-Johnson syndrome is a milder disease characterized by destruction and detachment of the skin epithelium and mucous membranes involving less than 10% of the body surface area. Ocular symptoms include ulcerative conjunctivitis, keratitis, iritis, uveitis and sometimes blindness. It can be caused by a severe adverse reaction to particular types of medication, although Mycoplasma infections may induce some cases. Note=Allele B*15:02 is associated with susceptibility to Stevens-Johnson syndrome. [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/1B15_HUMAN 1B15_HUMAN]] Involved in the presentation of foreign antigens to the immune system. [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The identification of recurrent human leukocyte antigen (HLA) neoepitopes driving T cell responses against tumors poses a significant bottleneck in the development of approaches for precision cancer therapeutics. Here, we employ a bioinformatics method, Prediction of T Cell Epitopes for Cancer Therapy, to analyze sequencing data from neuroblastoma patients and identify a recurrent anaplastic lymphoma kinase mutation (ALK R1275Q) that leads to two high affinity neoepitopes when expressed in complex with common HLA alleles. Analysis of the X-ray structures of the two peptides bound to HLA-B15:01 reveals drastically different conformations with measurable changes in the stability of the protein complexes, while the self-epitope is excluded from binding due to steric hindrance in the MHC groove. To evaluate the range of HLA alleles that could display the ALK neoepitopes, we used structure-based Rosetta comparative modeling calculations, which accurately predict several additional high affinity interactions and compare our results with commonly used prediction tools. Subsequent determination of the X-ray structure of an HLA-A01:01 bound neoepitope validates atomic features seen in our Rosetta models with respect to key residues relevant for MHC stability and T cell receptor recognition. Finally, MHC tetramer staining of peripheral blood mononuclear cells from HLA-matched donors shows that the two neoepitopes are recognized by CD8+ T cells. This work provides a rational approach toward high-throughput identification and further optimization of putative neoantigen/HLA targets with desired recognition features for cancer immunotherapy.

-	~~Authors: Toor, J~~., Rao, ~~A.A.~~, ~~Salama~~, S., ~~Tripathi~~, S., ~~Haussler~~, D., Sgourakis~~, N~~.G.	+	A Recurrent Mutation in Anaplastic Lymphoma Kinase with Distinct Neoepitope Conformations.,Toor JS, Rao AA, McShan AC, Yarmarkovich M, Nerli S, Yamaguchi K, Madejska AA, Nguyen S, Tripathi S, Maris JM, Salama SR, Haussler D, Sgourakis NG Front Immunol. 2018 Jan 30;9:99. doi: 10.3389/fimmu.2018.00099. eCollection 2018. PMID:29441070<ref>PMID:29441070</ref>

-	~~Description: Crystal structure~~ of ~~an anaplastic lymphoma kinase-derived neuroblastoma tumor antigen bound to~~ the ~~Human Major Histocompatibility Complex Class I molecule HLA-B*1501~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Sgourakis, N.G~~]]	+	<div class="pdbe-citations 5vz5" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Haussler, D]]		[[Category: Haussler, D]]
		+	[[Category: Rao, A A]]
	[[Category: Salama, S]]		[[Category: Salama, S]]
-	[[Category: ~~Rao~~, ~~A.A~~]]	+	[[Category: Sgourakis, N G]]
	[[Category: Toor, J]]		[[Category: Toor, J]]
	[[Category: Tripathi, S]]		[[Category: Tripathi, S]]
		+	[[Category: Complex]]
		+	[[Category: Human major histocompatibility complex class i]]
		+	[[Category: Immune system]]
		+	[[Category: Lymphoma kinase-derived neuroblastoma tumor antigen]]
		+	[[Category: Mhc-i]]

OCA: Protected "5vz5" [edit=sysop:move=sysop]

2017-09-27T14:17:27Z

Protected "5vz5" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:17, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5vz5 is ON HOLD until Paper Publication Authors: Toor, J., Rao, A.A., Salama, S., Tripathi, S., Haussler, D., Sgourakis, N.G. Description: Crystal ...

2017-09-27T14:17:26Z

New page: '''Unreleased structure''' The entry 5vz5 is ON HOLD until Paper Publication Authors: Toor, J., Rao, A.A., Salama, S., Tripathi, S., Haussler, D., Sgourakis, N.G. Description: Crystal ...

New page

'''Unreleased structure'''

The entry 5vz5 is ON HOLD until Paper Publication

Authors: Toor, J., Rao, A.A., Salama, S., Tripathi, S., Haussler, D., Sgourakis, N.G.

Description: Crystal structure of an anaplastic lymphoma kinase-derived neuroblastoma tumor antigen bound to the Human Major Histocompatibility Complex Class I molecule HLA-B*1501
[[Category: Unreleased Structures]]
[[Category: Sgourakis, N.G]]
[[Category: Haussler, D]]
[[Category: Salama, S]]
[[Category: Rao, A.A]]
[[Category: Toor, J]]
[[Category: Tripathi, S]]