4x6d

From Proteopedia

(Difference between revisions)

Revision as of 07:00, 29 May 2019

CD1a ternary complex with endogenous lipids and BK6 TCR

Structural highlights

4x6d is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	4x6c, 4x6b, 4x6e, 4x6f
Gene:	CD1A (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

[CD1A_HUMAN] Antigen-presenting protein that binds self and non-self lipid and glycolipid antigens and presents them to T-cell receptors on natural killer T-cells.^[15] ^[16] ^[17] [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

A central paradigm in alphabeta T cell-mediated immunity is the simultaneous co-recognition of antigens and antigen-presenting molecules by the alphabeta T cell antigen receptor (TCR). CD1a presents a broad repertoire of lipid-based antigens. We found that a prototypical autoreactive TCR bound CD1a when it was presenting a series of permissive endogenous ligands, while other lipid ligands were nonpermissive to TCR binding. The structures of two TCR-CD1a-lipid complexes showed that the TCR docked over the A' roof of CD1a in a manner that precluded direct contact with permissive ligands. Nonpermissive ligands indirectly inhibited TCR binding by disrupting the TCR-CD1a contact zone. The exclusive recognition of CD1a by the TCR represents a previously unknown mechanism whereby alphabeta T cells indirectly sense self antigens that are bound to an antigen-presenting molecule.

alphabeta T cell antigen receptor recognition of CD1a presenting self lipid ligands.,Birkinshaw RW, Pellicci DG, Cheng TY, Keller AN, Sandoval-Romero M, Gras S, de Jong A, Uldrich AP, Moody DB, Godfrey DI, Rossjohn J Nat Immunol. 2015 Mar;16(3):258-266. doi: 10.1038/ni.3098. Epub 2015 Feb 2. PMID:25642819^[18]

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
↑ Salamero J, Bausinger H, Mommaas AM, Lipsker D, Proamer F, Cazenave JP, Goud B, de la Salle H, Hanau D. CD1a molecules traffic through the early recycling endosomal pathway in human Langerhans cells. J Invest Dermatol. 2001 Mar;116(3):401-8. PMID:11231314 doi:1264
↑ Vincent MS, Xiong X, Grant EP, Peng W, Brenner MB. CD1a-, b-, and c-restricted TCRs recognize both self and foreign antigens. J Immunol. 2005 Nov 15;175(10):6344-51. PMID:16272286
↑ Sloma I, Zilber MT, Vasselon T, Setterblad N, Cavallari M, Mori L, De Libero G, Charron D, Mooney N, Gelin C. Regulation of CD1a surface expression and antigen presentation by invariant chain and lipid rafts. J Immunol. 2008 Jan 15;180(2):980-7. PMID:18178838
↑ Birkinshaw RW, Pellicci DG, Cheng TY, Keller AN, Sandoval-Romero M, Gras S, de Jong A, Uldrich AP, Moody DB, Godfrey DI, Rossjohn J. alphabeta T cell antigen receptor recognition of CD1a presenting self lipid ligands. Nat Immunol. 2015 Mar;16(3):258-266. doi: 10.1038/ni.3098. Epub 2015 Feb 2. PMID:25642819 doi:http://dx.doi.org/10.1038/ni.3098

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4x6d"

@@ Line 1: / Line 1: @@
 ==CD1a ternary complex with endogenous lipids and BK6 TCR==
-<StructureSection load='4x6d' size='340' side='right' caption='[[4x6d]], [[Resolution|resolution]] 2.98&Aring;' scene=''>
+<StructureSection load='4x6d' size='340' side='right'caption='[[4x6d]], [[Resolution|resolution]] 2.98&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4x6d]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X6D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X6D FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4x6d]] is a 8 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=4X6D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X6D FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=PAM:PALMITOLEIC+ACID'>PAM</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=PAM:PALMITOLEIC+ACID'>PAM</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4x6c|4x6c]], [[4x6b|4x6b]], [[4x6e|4x6e]], [[4x6f|4x6f]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD1A ([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=4x6d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x6d OCA], [http://pdbe.org/4x6d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x6d RCSB], [http://www.ebi.ac.uk/pdbsum/4x6d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x6d ProSAT]</span></td></tr>
 </table>
@@ Line 23: / Line 24: @@
 ==See Also==
-*[[Beta-2 microglobulin|Beta-2 microglobulin]]
+*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
+*[[T-cell receptor|T-cell receptor]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Birkinshaw, R W]]
 [[Category: Rossjohn, J]]

4x6d

From Proteopedia

Revision as of 07:00, 29 May 2019

CD1a ternary complex with endogenous lipids and BK6 TCR

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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