6pbh

From Proteopedia

(Difference between revisions)

Revision as of 16:43, 22 January 2020

Crystal Structure of HLA-A*68:01 in complex with NP145-156, a 12 mer influenza peptide

Structural highlights

6pbh is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	HLA-A, HLAA (HUMAN), B2M, CDABP0092, HDCMA22P (HUMAN)
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

[1A68_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

Although influenza viruses lead to severe illness in high-risk populations, host genetic factors associated with severe disease are largely unknown. As the HLA-A*68:01 allele can be linked to severe pandemic 2009-H1N1 disease, we investigate a potential impairment of HLA-A*68:01-restricted CD8(+) T cells to mount robust responses. We elucidate the HLA-A*68:01(+)CD8(+) T cell response directed toward an extended influenza-derived nucleoprotein (NP) peptide and show that only ~35% individuals have immunodominant A68/NP145(+)CD8(+) T cell responses. Dissecting A68/NP145(+)CD8(+) T cells in low vs. medium/high responders reveals that high responding donors have A68/NP145(+)CD8(+) memory T cells with clonally expanded TCRalphabetas, while low-responders display A68/NP145(+)CD8(+) T cells with predominantly naive phenotypes and non-expanded TCRalphabetas. Single-cell index sorting and TCRalphabeta analyses link expansion of A68/NP145(+)CD8(+) T cells to their memory potential. Our study demonstrates the immunodominance potential of influenza-specific CD8(+) T cells presented by a risk HLA-A*68:01 molecule and advocates for priming CD8(+) T cell compartments in HLA-A*68:01-expressing individuals for establishment of pre-existing protective memory T cell pools.

Challenging immunodominance of influenza-specific CD8(+) T cell responses restricted by the risk-associated HLA-A*68:01 allomorph.,van de Sandt CE, Clemens EB, Grant EJ, Rowntree LC, Sant S, Halim H, Crowe J, Cheng AC, Kotsimbos TC, Richards M, Miller A, Tong SYC, Rossjohn J, Nguyen THO, Gras S, Chen W, Kedzierska K Nat Commun. 2019 Dec 6;10(1):5579. doi: 10.1038/s41467-019-13346-4. PMID:31811120^[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
↑ van de Sandt CE, Clemens EB, Grant EJ, Rowntree LC, Sant S, Halim H, Crowe J, Cheng AC, Kotsimbos TC, Richards M, Miller A, Tong SYC, Rossjohn J, Nguyen THO, Gras S, Chen W, Kedzierska K. Challenging immunodominance of influenza-specific CD8(+) T cell responses restricted by the risk-associated HLA-A*68:01 allomorph. Nat Commun. 2019 Dec 6;10(1):5579. doi: 10.1038/s41467-019-13346-4. PMID:31811120 doi:http://dx.doi.org/10.1038/s41467-019-13346-4

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/6pbh"

@@ Line 3: / Line 3: @@
 <StructureSection load='6pbh' size='340' side='right'caption='[[6pbh]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6pbh]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PBH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PBH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6pbh]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PBH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PBH FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HLA-A, HLAA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), B2M, CDABP0092, HDCMA22P ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6pbh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pbh OCA], [http://pdbe.org/6pbh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pbh RCSB], [http://www.ebi.ac.uk/pdbsum/6pbh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pbh ProSAT]</span></td></tr>
 </table>
@@ Line 11: / Line 12: @@
 == Function ==
 [[http://www.uniprot.org/uniprot/1A68_HUMAN 1A68_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 ==
+Although influenza viruses lead to severe illness in high-risk populations, host genetic factors associated with severe disease are largely unknown. As the HLA-A*68:01 allele can be linked to severe pandemic 2009-H1N1 disease, we investigate a potential impairment of HLA-A*68:01-restricted CD8(+) T cells to mount robust responses. We elucidate the HLA-A*68:01(+)CD8(+) T cell response directed toward an extended influenza-derived nucleoprotein (NP) peptide and show that only ~35% individuals have immunodominant A68/NP145(+)CD8(+) T cell responses. Dissecting A68/NP145(+)CD8(+) T cells in low vs. medium/high responders reveals that high responding donors have A68/NP145(+)CD8(+) memory T cells with clonally expanded TCRalphabetas, while low-responders display A68/NP145(+)CD8(+) T cells with predominantly naive phenotypes and non-expanded TCRalphabetas. Single-cell index sorting and TCRalphabeta analyses link expansion of A68/NP145(+)CD8(+) T cells to their memory potential. Our study demonstrates the immunodominance potential of influenza-specific CD8(+) T cells presented by a risk HLA-A*68:01 molecule and advocates for priming CD8(+) T cell compartments in HLA-A*68:01-expressing individuals for establishment of pre-existing protective memory T cell pools.
+Challenging immunodominance of influenza-specific CD8(+) T cell responses restricted by the risk-associated HLA-A*68:01 allomorph.,van de Sandt CE, Clemens EB, Grant EJ, Rowntree LC, Sant S, Halim H, Crowe J, Cheng AC, Kotsimbos TC, Richards M, Miller A, Tong SYC, Rossjohn J, Nguyen THO, Gras S, Chen W, Kedzierska K Nat Commun. 2019 Dec 6;10(1):5579. doi: 10.1038/s41467-019-13346-4. PMID:31811120<ref>PMID:31811120</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6pbh" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Gras, S]]

6pbh

From Proteopedia

Revision as of 16:43, 22 January 2020

Crystal Structure of HLA-A*68:01 in complex with NP145-156, a 12 mer influenza peptide

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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