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2x4r

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Crystal structure of MHC CLass I HLA-A2.1 bound to Cytomegalovirus (CMV) pp65 epitope

Structural highlights

2x4r is a 6 chain structure with sequence from Homo sapiens and Human betaherpesvirus 5. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Ligands:
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

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

High-throughput structure determination of protein-ligand complexes is central in drug development and structural proteomics. To facilitate such high-throughput structure determination we designed an induced replacement strategy. Crystals of a protein complex bound to a photosensitive ligand are exposed to UV light, inducing the departure of the bound ligand, allowing a new ligand to soak in. We exemplify the approach for a class of protein complexes that is especially recalcitrant to high-throughput strategies: the MHC class I proteins. We developed a UV-sensitive, "conditional", peptide ligand whose UV-induced cleavage in the crystals leads to the exchange of the low-affinity lytic fragments for full-length peptides introduced in the crystallant solution. This "in crystallo" exchange is monitored by the loss of seleno-methionine anomalous diffraction signal of the conditional peptide compared to the signal of labeled MHC beta2m subunit. This method has the potential to facilitate high-throughput crystallography in various protein families.

UV-induced ligand exchange in MHC class I protein crystals.,Celie PH, Toebes M, Rodenko B, Ovaa H, Perrakis A, Schumacher TN J Am Chem Soc. 2009 Sep 2;131(34):12298-304. PMID:19655750^[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
↑ Celie PH, Toebes M, Rodenko B, Ovaa H, Perrakis A, Schumacher TN. UV-induced ligand exchange in MHC class I protein crystals. J Am Chem Soc. 2009 Sep 2;131(34):12298-304. PMID:19655750 doi:10.1021/ja9037559

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/2x4r"

@@ Line 3: / Line 3: @@
 <StructureSection load='2x4r' size='340' side='right'caption='[[2x4r]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2x4r]] is a 6 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=2X4R OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2X4R FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2x4r]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_betaherpesvirus_5 Human betaherpesvirus 5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X4R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X4R 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></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]] 2.3&#8491;</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]], [[2esv|2esv]], [[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]], [[2vlk|2vlk]], [[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]], [[1a9e|1a9e]], [[1duz|1duz]], [[2clr|2clr]], [[3hla|3hla]], [[1m05|1m05]], [[1tvb|1tvb]], [[2v2w|2v2w]], [[1onq|1onq]], [[2vlr|2vlr]], [[2bvo|2bvo]], [[1a1n|1a1n]], [[1lp9|1lp9]], [[1zsd|1zsd]], [[1m6o|1m6o]], [[1hhk|1hhk]], [[1hsb|1hsb]], [[1zt4|1zt4]], [[1x7q|1x7q]], [[1ce6|1ce6]], [[1py4|1py4]], [[1syv|1syv]], [[2j8u|2j8u]], [[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]], [[2bvp|2bvp]], [[2v2x|2v2x]], [[1xr9|1xr9]], [[2gj6|2gj6]], [[1qlf|1qlf]], [[1efx|1efx]], [[2av1|2av1]], [[1tmc|1tmc]], [[1qsf|1qsf]], [[1duy|1duy]], [[1kpr|1kpr]], [[1jge|1jge]], [[2hjl|2hjl]], [[1qew|1qew]], [[1w0v|1w0v]], [[1k5n|1k5n]], [[1ao7|1ao7]], [[2bnr|2bnr]], [[1xh3|1xh3]], [[2bst|2bst]], [[1mi5|1mi5]], [[2h26|2h26]], [[1s9y|1s9y]], [[1a1o|1a1o]], [[2a83|2a83]], [[1agf|1agf]], [[1oga|1oga]], [[2f8o|2f8o]], [[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]], [[1ydp|1ydp]], [[1i4f|1i4f]], [[2vll|2vll]], [[2bsr|2bsr]], [[1of2|1of2]], [[1b0g|1b0g]], [[2vlj|2vlj]], [[1b0r|1b0r]], [[1hhi|1hhi]], [[1qse|1qse]], [[2axg|2axg]], [[1a9b|1a9b]], [[2bvq|2bvq]], [[1agc|1agc]], [[1hhj|1hhj]], [[1qvo|1qvo]], [[1s9w|1s9w]], [[1ktl|1ktl]], [[1a6z|1a6z]], [[2cik|2cik]], [[1i1f|1i1f]], [[2uwe|2uwe]], [[2av7|2av7]], [[2x4p|2x4p]], [[2x4u|2x4u]], [[2x4s|2x4s]], [[2x4t|2x4t]], [[2x4n|2x4n]], [[2x4o|2x4o]], [[2x4q|2x4q]]</div></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></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=2x4r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x4r OCA], [http://pdbe.org/2x4r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2x4r RCSB], [http://www.ebi.ac.uk/pdbsum/2x4r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2x4r 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=2x4r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x4r OCA], [https://pdbe.org/2x4r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x4r RCSB], [https://www.ebi.ac.uk/pdbsum/2x4r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x4r ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[https://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/1A02_HUMAN 1A02_HUMAN]] Involved in the presentation of foreign antigens to the immune system. [[http://www.uniprot.org/uniprot/PP65_HCMVA PP65_HCMVA]] Counteracts the host antiviral immune response when activated and phosphorylated, by preventing IRF3 from entering the nucleus. Also participates in the transactivation of viral major immediate-early genes by the recruitment of host IFI16 to the promoters pf these genes.<ref>PMID:15452220</ref> <ref>PMID:20504932</ref>
+[https://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.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 35: @@
 *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
 *[[MHC 3D structures|MHC 3D structures]]
+*[[MHC I 3D structures|MHC I 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
+[[Category: Human betaherpesvirus 5]]
 [[Category: Large Structures]]
-[[Category: Celie, P H.N]]
+[[Category: Celie PHN]]
-[[Category: Ovaa, H]]
+[[Category: Ovaa H]]
-[[Category: Perrakis, A]]
+[[Category: Perrakis A]]
-[[Category: Rodenko, B]]
+[[Category: Rodenko B]]
-[[Category: Schumacher, T N.M]]
+[[Category: Schumacher TNM]]
-[[Category: Toebes, M]]
+[[Category: Toebes M]]
-[[Category: Amyloid]]
-[[Category: Amyloidosis]]
-[[Category: Glycation]]
-[[Category: Host-virus interaction]]
-[[Category: Immune response]]
-[[Category: Immune system]]
-[[Category: Immunoglobulin domain]]
-[[Category: Photocleavable peptide]]

2x4r

From Proteopedia

Current revision

Crystal structure of MHC CLass I HLA-A2.1 bound to Cytomegalovirus (CMV) pp65 epitope

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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