6bxp

From Proteopedia

(Difference between revisions)

Revision as of 06:30, 14 March 2018

Crystal Structure of HLA-B*57:01 with a modified HIV peptide RKV-Kyn

Structural highlights

6bxp is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[B2MG_HUMAN] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:241600]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.^[1] 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.^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14]

Function

[1B57_HUMAN] Involved in the presentation of foreign antigens to the immune system. [B2MG_HUMAN] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.

Publication Abstract from PubMed

The recognition of pathogen-derived peptides by T lymphocytes is the cornerstone of adaptive immunity, whereby intracellular antigens are degraded in the cytosol and short peptides assemble with class I human leukocyte antigen (HLA) molecules in the endoplasmic reticulum (ER). These peptide-HLA complexes egress to the cell surface and are scrutinized by cytotoxic CD8+ T-cells leading to the eradication of the infected cell. Here we identify naturally presented HLA-B*57:01 bound peptides derived from the envelope protein of the human immunodeficiency virus (HIVenv). HIVenv peptides were present at a very small percentage of the overall HLA-B*57:01 peptidome (<0.1%) and both native and post-translationally modified forms of two distinct HIV peptides were identified. Notably, a peptide bearing a natively encoded C-terminal tryptophan residue was also present in a modified form containing a kynurenine residue. Kynurenine is a major product of tryptophan catabolism and is abundant during inflammation and infection. We examined the binding of these peptides at a molecular level and examine their immunogenicity in preliminary functional studies. Modest immune responses were observed to the modified HIVenv peptide, highlighting a potential role for kynurenine-modified peptides in the immune response to HIV and other viral infections. This article is protected by copyright. All rights reserved.

Identification of Native and Post-Translationally Modified HLA-B*57:01-Restricted HIV Envelope Derived Epitopes Using Immunoproteomics.,Ramarathinam SH, Gras S, Alcantara S, Yeung AWS, Mifsud NA, Sonza S, Illing PT, Glaros EN, Center RJ, Thomas S, Kent SJ, Ternette N, Purcell DFJ, Rossjohn J, Purcell AW Proteomics. 2018 Feb 13. doi: 10.1002/pmic.201700253. PMID:29437277^[15]

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

References

↑ Wani MA, Haynes LD, Kim J, Bronson CL, Chaudhury C, Mohanty S, Waldmann TA, Robinson JM, Anderson CL. Familial hypercatabolic hypoproteinemia caused by deficiency of the neonatal Fc receptor, FcRn, due to a mutant beta2-microglobulin gene. Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5084-9. Epub 2006 Mar 20. PMID:16549777 doi:10.1073/pnas.0600548103
↑ Gorevic PD, Munoz PC, Casey TT, DiRaimondo CR, Stone WJ, Prelli FC, Rodrigues MM, Poulik MD, Frangione B. Polymerization of intact beta 2-microglobulin in tissue causes amyloidosis in patients on chronic hemodialysis. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7908-12. PMID:3532124
↑ Argiles A, Derancourt J, Jauregui-Adell J, Mion C, Demaille JG. Biochemical characterization of serum and urinary beta 2 microglobulin in end-stage renal disease patients. Nephrol Dial Transplant. 1992;7(11):1106-10. PMID:1336137
↑ Momoi T, Suzuki M, Titani K, Hisanaga S, Ogawa H, Saito A. Amino acid sequence of a modified beta 2-microglobulin in renal failure patient urine and long-term dialysis patient blood. Clin Chim Acta. 1995 May 15;236(2):135-44. PMID:7554280
↑ Cunningham BA, Wang JL, Berggard I, Peterson PA. The complete amino acid sequence of beta 2-microglobulin. Biochemistry. 1973 Nov 20;12(24):4811-22. PMID:4586824
↑ Haag-Weber M, Mai B, Horl WH. Isolation of a granulocyte inhibitory protein from uraemic patients with homology of beta 2-microglobulin. Nephrol Dial Transplant. 1994;9(4):382-8. PMID:8084451
↑ Trinh CH, Smith DP, Kalverda AP, Phillips SE, Radford SE. Crystal structure of monomeric human beta-2-microglobulin reveals clues to its amyloidogenic properties. Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9771-6. Epub 2002 Jul 15. PMID:12119416 doi:10.1073/pnas.152337399
↑ Stewart-Jones GB, McMichael AJ, Bell JI, Stuart DI, Jones EY. A structural basis for immunodominant human T cell receptor recognition. Nat Immunol. 2003 Jul;4(7):657-63. Epub 2003 Jun 8. PMID:12796775 doi:10.1038/ni942
↑ Kihara M, Chatani E, Iwata K, Yamamoto K, Matsuura T, Nakagawa A, Naiki H, Goto Y. Conformation of amyloid fibrils of beta2-microglobulin probed by tryptophan mutagenesis. J Biol Chem. 2006 Oct 13;281(41):31061-9. Epub 2006 Aug 10. PMID:16901902 doi:10.1074/jbc.M605358200
↑ Eakin CM, Berman AJ, Miranker AD. A native to amyloidogenic transition regulated by a backbone trigger. Nat Struct Mol Biol. 2006 Mar;13(3):202-8. Epub 2006 Feb 19. PMID:16491088 doi:10.1038/nsmb1068
↑ Iwata K, Matsuura T, Sakurai K, Nakagawa A, Goto Y. High-resolution crystal structure of beta2-microglobulin formed at pH 7.0. J Biochem. 2007 Sep;142(3):413-9. Epub 2007 Jul 23. PMID:17646174 doi:10.1093/jb/mvm148
↑ Ricagno S, Colombo M, de Rosa M, Sangiovanni E, Giorgetti S, Raimondi S, Bellotti V, Bolognesi M. DE loop mutations affect beta2-microglobulin stability and amyloid aggregation. Biochem Biophys Res Commun. 2008 Dec 5;377(1):146-50. Epub 2008 Oct 1. PMID:18835253 doi:S0006-291X(08)01866-4
↑ Esposito G, Ricagno S, Corazza A, Rennella E, Gumral D, Mimmi MC, Betto E, Pucillo CE, Fogolari F, Viglino P, Raimondi S, Giorgetti S, Bolognesi B, Merlini G, Stoppini M, Bolognesi M, Bellotti V. The controlling roles of Trp60 and Trp95 in beta2-microglobulin function, folding and amyloid aggregation properties. J Mol Biol. 2008 May 9;378(4):887-97. Epub 2008 Mar 8. PMID:18395224 doi:10.1016/j.jmb.2008.03.002
↑ Ricagno S, Raimondi S, Giorgetti S, Bellotti V, Bolognesi M. Human beta-2 microglobulin W60V mutant structure: Implications for stability and amyloid aggregation. Biochem Biophys Res Commun. 2009 Mar 13;380(3):543-7. Epub 2009 Jan 25. PMID:19284997 doi:10.1016/j.bbrc.2009.01.116
↑ Ramarathinam SH, Gras S, Alcantara S, Yeung AWS, Mifsud NA, Sonza S, Illing PT, Glaros EN, Center RJ, Thomas S, Kent SJ, Ternette N, Purcell DFJ, Rossjohn J, Purcell AW. Identification of Native and Post-Translationally Modified HLA-B*57:01-Restricted HIV Envelope Derived Epitopes Using Immunoproteomics. Proteomics. 2018 Feb 13. doi: 10.1002/pmic.201700253. PMID:29437277 doi:http://dx.doi.org/10.1002/pmic.201700253

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6bxp"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6bxp is ON HOLD
+==Crystal Structure of HLA-B*57:01 with a modified HIV peptide RKV-Kyn==
+<StructureSection load='6bxp' size='340' side='right' caption='[[6bxp]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6bxp]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BXP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BXP FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr>
+<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KYN:(2S)-2-AMINO-4-(2-AMINOPHENYL)-4-OXOBUTANOIC+ACID'>KYN</scene></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=6bxp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bxp OCA], [http://pdbe.org/6bxp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bxp RCSB], [http://www.ebi.ac.uk/pdbsum/6bxp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bxp ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[[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/1B57_HUMAN 1B57_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 recognition of pathogen-derived peptides by T lymphocytes is the cornerstone of adaptive immunity, whereby intracellular antigens are degraded in the cytosol and short peptides assemble with class I human leukocyte antigen (HLA) molecules in the endoplasmic reticulum (ER). These peptide-HLA complexes egress to the cell surface and are scrutinized by cytotoxic CD8+ T-cells leading to the eradication of the infected cell. Here we identify naturally presented HLA-B*57:01 bound peptides derived from the envelope protein of the human immunodeficiency virus (HIVenv). HIVenv peptides were present at a very small percentage of the overall HLA-B*57:01 peptidome (&lt;0.1%) and both native and post-translationally modified forms of two distinct HIV peptides were identified. Notably, a peptide bearing a natively encoded C-terminal tryptophan residue was also present in a modified form containing a kynurenine residue. Kynurenine is a major product of tryptophan catabolism and is abundant during inflammation and infection. We examined the binding of these peptides at a molecular level and examine their immunogenicity in preliminary functional studies. Modest immune responses were observed to the modified HIVenv peptide, highlighting a potential role for kynurenine-modified peptides in the immune response to HIV and other viral infections. This article is protected by copyright. All rights reserved.
-Authors:
+Identification of Native and Post-Translationally Modified HLA-B*57:01-Restricted HIV Envelope Derived Epitopes Using Immunoproteomics.,Ramarathinam SH, Gras S, Alcantara S, Yeung AWS, Mifsud NA, Sonza S, Illing PT, Glaros EN, Center RJ, Thomas S, Kent SJ, Ternette N, Purcell DFJ, Rossjohn J, Purcell AW Proteomics. 2018 Feb 13. doi: 10.1002/pmic.201700253. PMID:29437277<ref>PMID:29437277</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 6bxp" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Gras, S]]
+[[Category: Rossjohn, J]]
+[[Category: Hiv]]
+[[Category: Hla-b*57:01]]
+[[Category: Immune system]]
+[[Category: Immunopeptidome]]
+[[Category: Kynurenine]]
+[[Category: Ptm]]

6bxp

From Proteopedia

Revision as of 06:30, 14 March 2018

Crystal Structure of HLA-B*57:01 with a modified HIV peptide RKV-Kyn

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox