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2j8u

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Revision as of 21:24, 18 November 2020

Large CDR3a loop alteration as a function of MHC mutation.

Structural highlights

2j8u is a 10 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1uqs, 1bd2, 2ak4, 1ypz, 1im3, 1uxw, 1i7u, 1c16, 1hsa, 2axf, 1gzp, 2bnq, 1w72, 2jcc, 2bck, 1de4, 1n2r, 1exu, 1qrn, 2hla, 1mhe, 1im9, 1eez, 1jht, 1qqd, 1qr1, 1zs8, 1hla, 1jgd, 1i1y, 1vgk, 1age, 1ur7, 1hhg, 1s9x, 1duz, 1a9e, 2clr, 3hla, 1m05, 1tvb, 2v2w, 1onq, 1a1n, 1lp9, 1zsd, 1m6o, 2bsu, 1hhk, 1zt4, 1hsb, 1x7q, 1ce6, 1py4, 1syv, 1sys, 1ogt, 1cg9, 1p7q, 1q94, 1jnj, 1agb, 2d31, 1aqd, 1xz0, 1lds, 1hhh, 1tvh, 1xr8, 2bss, 1e28, 1a1m, 2v2x, 1xr9, 2gj6, 1efx, 1qlf, 2av1, 1tmc, 1qsf, 1duy, 1jge, 1kpr, 2hjl, 1qew, 1w0v, 1k5n, 1ao7, 2bnr, 1xh3, 2bst, 1mi5, 2h26, 1s9y, 1a1o, 1agf, 2a83, 1oga, 2f8o, 2bsv, 2cii, 1i7r, 1jf1, 2c7u, 2f74, 1e27, 1w0w, 1gzq, 1uxs, 1akj, 2hjk, 2vb5, 1agd, 1r3h, 1eey, 1i7t, 1i4f, 1ydp, 2bsr, 1b0g, 1b0r, 1of2, 1hhi, 1qse, 1a9b, 2axg, 1agc, 2bvq, 1hhj, 1qvo, 1s9w, 1ktl, 1a6z, 2cik, 2uwe, 1i1f, 2av7
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

[1A02_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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The keystone of the adaptive immune response is T cell receptor (TCR) recognition of peptide presented by major histocompatibility complex (pMHC) molecules. The crystal structure of AHIII TCR bound to MHC, HLA-A2, showed a large interface with an atypical binding orientation. MHC mutations in the interface of the proteins were tested for changes in TCR recognition. From the range of responses observed, three representative HLA-A2 mutants, T163A, W167A, and K66A, were selected for further study. Binding constants and co-crystal structures of the AHIII TCR and the three mutants were determined. K66 in HLA-A2 makes contacts with both peptide and TCR, and has been identified as a critical residue for recognition by numerous TCR. The K66A mutation resulted in the lowest AHIII T cell response and the lowest binding affinity, which suggests that the T cell response may correlate with affinity. Importantly, the K66A mutation does not affect the conformation of the peptide. The change in affinity appears to be due to a loss in hydrogen bonds in the interface as a result of a conformational change in the TCR complementarity-determining region 3 (CDR3) loop. Isothermal titration calorimetry confirmed the loss of hydrogen bonding by a large loss in enthalpy. Our findings are inconsistent with the notion that the CDR1 and CDR2 loops of the TCR are responsible for MHC restriction, while the CDR3 loops interact solely with the peptide. Instead, we present here an MHC mutation that does not change the conformation of the peptide, yet results in an altered conformation of a CDR3.

Single MHC mutation eliminates enthalpy associated with T cell receptor binding.,Miller PJ, Pazy Y, Conti B, Riddle D, Appella E, Collins EJ J Mol Biol. 2007 Oct 19;373(2):315-27. Epub 2007 Jul 26. PMID:17825839^[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
↑ Miller PJ, Pazy Y, Conti B, Riddle D, Appella E, Collins EJ. Single MHC mutation eliminates enthalpy associated with T cell receptor binding. J Mol Biol. 2007 Oct 19;373(2):315-27. Epub 2007 Jul 26. PMID:17825839 doi:10.1016/j.jmb.2007.07.028

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2j8u"

@@ Line 1: / Line 1: @@
 ==Large CDR3a loop alteration as a function of MHC mutation.==
-<StructureSection load='2j8u' size='340' side='right' caption='[[2j8u]], [[Resolution|resolution]] 2.88&Aring;' scene=''>
+<StructureSection load='2j8u' size='340' side='right'caption='[[2j8u]], [[Resolution|resolution]] 2.88&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2j8u]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J8U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J8U FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2j8u]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J8U OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2J8U FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1uqs|1uqs]], [[1bd2|1bd2]], [[2ak4|2ak4]], [[1ypz|1ypz]], [[1im3|1im3]], [[1uxw|1uxw]], [[1i7u|1i7u]], [[1c16|1c16]], [[1hsa|1hsa]], [[2axf|2axf]], [[1gzp|1gzp]], [[2bnq|2bnq]], [[1w72|1w72]], [[2jcc|2jcc]], [[2bck|2bck]], [[1de4|1de4]], [[1n2r|1n2r]], [[1exu|1exu]], [[1qrn|1qrn]], [[2hla|2hla]], [[1mhe|1mhe]], [[1im9|1im9]], [[1eez|1eez]], [[1jht|1jht]], [[1qqd|1qqd]], [[1qr1|1qr1]], [[1zs8|1zs8]], [[1hla|1hla]], [[1jgd|1jgd]], [[1i1y|1i1y]], [[1vgk|1vgk]], [[1age|1age]], [[1ur7|1ur7]], [[1hhg|1hhg]], [[1s9x|1s9x]], [[1duz|1duz]], [[1a9e|1a9e]], [[2clr|2clr]], [[3hla|3hla]], [[1m05|1m05]], [[1tvb|1tvb]], [[2v2w|2v2w]], [[1onq|1onq]], [[1a1n|1a1n]], [[1lp9|1lp9]], [[1zsd|1zsd]], [[1m6o|1m6o]], [[2bsu|2bsu]], [[1hhk|1hhk]], [[1zt4|1zt4]], [[1hsb|1hsb]], [[1x7q|1x7q]], [[1ce6|1ce6]], [[1py4|1py4]], [[1syv|1syv]], [[1sys|1sys]], [[1ogt|1ogt]], [[1cg9|1cg9]], [[1p7q|1p7q]], [[1q94|1q94]], [[1jnj|1jnj]], [[1agb|1agb]], [[2d31|2d31]], [[1aqd|1aqd]], [[1xz0|1xz0]], [[1lds|1lds]], [[1hhh|1hhh]], [[1tvh|1tvh]], [[1xr8|1xr8]], [[2bss|2bss]], [[1e28|1e28]], [[1a1m|1a1m]], [[2v2x|2v2x]], [[1xr9|1xr9]], [[2gj6|2gj6]], [[1efx|1efx]], [[1qlf|1qlf]], [[2av1|2av1]], [[1tmc|1tmc]], [[1qsf|1qsf]], [[1duy|1duy]], [[1jge|1jge]], [[1kpr|1kpr]], [[2hjl|2hjl]], [[1qew|1qew]], [[1w0v|1w0v]], [[1k5n|1k5n]], [[1ao7|1ao7]], [[2bnr|2bnr]], [[1xh3|1xh3]], [[2bst|2bst]], [[1mi5|1mi5]], [[2h26|2h26]], [[1s9y|1s9y]], [[1a1o|1a1o]], [[1agf|1agf]], [[2a83|2a83]], [[1oga|1oga]], [[2f8o|2f8o]], [[2bsv|2bsv]], [[2cii|2cii]], [[1i7r|1i7r]], [[1jf1|1jf1]], [[2c7u|2c7u]], [[2f74|2f74]], [[1e27|1e27]], [[1w0w|1w0w]], [[1gzq|1gzq]], [[1uxs|1uxs]], [[1akj|1akj]], [[2hjk|2hjk]], [[2vb5|2vb5]], [[1agd|1agd]], [[1r3h|1r3h]], [[1eey|1eey]], [[1i7t|1i7t]], [[1i4f|1i4f]], [[1ydp|1ydp]], [[2bsr|2bsr]], [[1b0g|1b0g]], [[1b0r|1b0r]], [[1of2|1of2]], [[1hhi|1hhi]], [[1qse|1qse]], [[1a9b|1a9b]], [[2axg|2axg]], [[1agc|1agc]], [[2bvq|2bvq]], [[1hhj|1hhj]], [[1qvo|1qvo]], [[1s9w|1s9w]], [[1ktl|1ktl]], [[1a6z|1a6z]], [[2cik|2cik]], [[2uwe|2uwe]], [[1i1f|1i1f]], [[2av7|2av7]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1uqs|1uqs]], [[1bd2|1bd2]], [[2ak4|2ak4]], [[1ypz|1ypz]], [[1im3|1im3]], [[1uxw|1uxw]], [[1i7u|1i7u]], [[1c16|1c16]], [[1hsa|1hsa]], [[2axf|2axf]], [[1gzp|1gzp]], [[2bnq|2bnq]], [[1w72|1w72]], [[2jcc|2jcc]], [[2bck|2bck]], [[1de4|1de4]], [[1n2r|1n2r]], [[1exu|1exu]], [[1qrn|1qrn]], [[2hla|2hla]], [[1mhe|1mhe]], [[1im9|1im9]], [[1eez|1eez]], [[1jht|1jht]], [[1qqd|1qqd]], [[1qr1|1qr1]], [[1zs8|1zs8]], [[1hla|1hla]], [[1jgd|1jgd]], [[1i1y|1i1y]], [[1vgk|1vgk]], [[1age|1age]], [[1ur7|1ur7]], [[1hhg|1hhg]], [[1s9x|1s9x]], [[1duz|1duz]], [[1a9e|1a9e]], [[2clr|2clr]], [[3hla|3hla]], [[1m05|1m05]], [[1tvb|1tvb]], [[2v2w|2v2w]], [[1onq|1onq]], [[1a1n|1a1n]], [[1lp9|1lp9]], [[1zsd|1zsd]], [[1m6o|1m6o]], [[2bsu|2bsu]], [[1hhk|1hhk]], [[1zt4|1zt4]], [[1hsb|1hsb]], [[1x7q|1x7q]], [[1ce6|1ce6]], [[1py4|1py4]], [[1syv|1syv]], [[1sys|1sys]], [[1ogt|1ogt]], [[1cg9|1cg9]], [[1p7q|1p7q]], [[1q94|1q94]], [[1jnj|1jnj]], [[1agb|1agb]], [[2d31|2d31]], [[1aqd|1aqd]], [[1xz0|1xz0]], [[1lds|1lds]], [[1hhh|1hhh]], [[1tvh|1tvh]], [[1xr8|1xr8]], [[2bss|2bss]], [[1e28|1e28]], [[1a1m|1a1m]], [[2v2x|2v2x]], [[1xr9|1xr9]], [[2gj6|2gj6]], [[1efx|1efx]], [[1qlf|1qlf]], [[2av1|2av1]], [[1tmc|1tmc]], [[1qsf|1qsf]], [[1duy|1duy]], [[1jge|1jge]], [[1kpr|1kpr]], [[2hjl|2hjl]], [[1qew|1qew]], [[1w0v|1w0v]], [[1k5n|1k5n]], [[1ao7|1ao7]], [[2bnr|2bnr]], [[1xh3|1xh3]], [[2bst|2bst]], [[1mi5|1mi5]], [[2h26|2h26]], [[1s9y|1s9y]], [[1a1o|1a1o]], [[1agf|1agf]], [[2a83|2a83]], [[1oga|1oga]], [[2f8o|2f8o]], [[2bsv|2bsv]], [[2cii|2cii]], [[1i7r|1i7r]], [[1jf1|1jf1]], [[2c7u|2c7u]], [[2f74|2f74]], [[1e27|1e27]], [[1w0w|1w0w]], [[1gzq|1gzq]], [[1uxs|1uxs]], [[1akj|1akj]], [[2hjk|2hjk]], [[2vb5|2vb5]], [[1agd|1agd]], [[1r3h|1r3h]], [[1eey|1eey]], [[1i7t|1i7t]], [[1i4f|1i4f]], [[1ydp|1ydp]], [[2bsr|2bsr]], [[1b0g|1b0g]], [[1b0r|1b0r]], [[1of2|1of2]], [[1hhi|1hhi]], [[1qse|1qse]], [[1a9b|1a9b]], [[2axg|2axg]], [[1agc|1agc]], [[2bvq|2bvq]], [[1hhj|1hhj]], [[1qvo|1qvo]], [[1s9w|1s9w]], [[1ktl|1ktl]], [[1a6z|1a6z]], [[2cik|2cik]], [[2uwe|2uwe]], [[1i1f|1i1f]], [[2av7|2av7]]</div></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=2j8u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j8u OCA], [http://pdbe.org/2j8u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j8u RCSB], [http://www.ebi.ac.uk/pdbsum/2j8u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2j8u 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=2j8u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j8u OCA], [http://pdbe.org/2j8u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j8u RCSB], [http://www.ebi.ac.uk/pdbsum/2j8u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2j8u ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 33: / Line 33: @@
 ==See Also==
-*[[Beta-2 microglobulin|Beta-2 microglobulin]]
+*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
-*[[Major histocompatibility complex|Major histocompatibility complex]]
+*[[MHC 3D structures|MHC 3D structures]]
-*[[T-cell receptor|T-cell receptor]]
+*[[T-cell receptor 3D structures|T-cell receptor 3D structures]]
 == References ==
 <references/>
@@ Line 41: / Line 41: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Lk3 transgenic mice]]
 [[Category: Benhar, Y P]]

2j8u

From Proteopedia

Revision as of 21:24, 18 November 2020

Large CDR3a loop alteration as a function of MHC mutation.

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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