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1xr9

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Revision as of 08:49, 8 January 2015

Crystal Structures of HLA-B*1501 in Complex with Peptides from Human UbcH6 and Epstein-Barr Virus EBNA-3

Structural highlights

1xr9 is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	1xr8
Gene:	HLA-Bw62.1 (Homo sapiens), B2M (Homo sapiens)
Activity:	Ubiquitin--protein ligase, with EC number 6.3.2.19
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[1B15_HUMAN] Defects in HLA-B are a cause of susceptibility to Stevens-Johnson syndrome (SJS) [MIM:608579]. A rare blistering mucocutaneous disease that share clinical and histopathologic features with toxic epidermal necrolysis. Both disorders are characterized by high fever, malaise, and a rapidly developing blistering exanthema of macules and target-like lesions accompanied by mucosal involvement. Stevens-Johnson syndrome is a milder disease characterized by destruction and detachment of the skin epithelium and mucous membranes involving less than 10% of the body surface area. Ocular symptoms include ulcerative conjunctivitis, keratitis, iritis, uveitis and sometimes blindness. It can be caused by a severe adverse reaction to particular types of medication, although Mycoplasma infections may induce some cases. Note=Allele B*15:02 is associated with susceptibility to Stevens-Johnson syndrome. [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

[1B15_HUMAN] Involved in the presentation of foreign antigens to the immune system. [UB2E1_HUMAN] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes the covalent attachment of ISG15 to other proteins. Mediates the selective degradation of short-lived and abnormal proteins. In vitro also catalyzes 'Lys-48'-linked polyubiquitination.^[15] ^[16] [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

MHC class I molecules govern human cytotoxic T cell responses. Their specificity determines which peptides they sample from the intracellular protein environment and then present to human cytotoxic T cells. More than 1100 different MHC class I proteins have been found in human populations and it would be a major undertaking to address each of these specificities individually. Based upon their peptide binding specificity, they are currently subdivided into 12 supertypes. Several of these HLA supertypes have not yet been described at the structural level. To support a comprehensive understanding of human immune responses, the structure of at least one member of each supertype should be determined. Here, the structures of two immunogenic peptide-HLA-B*1501 complexes are described. The structure of HLA-B*1501 in complex with a peptide (LEKARGSTY, corresponding to positions 274-282 in the Epstein-Barr virus nuclear antigen-3A) was determined to 2.3 A resolution. The structure of HLA-B*1501 in complex with a peptide (ILGPPGSVY) derived from human ubiquitin-conjugating enzyme-E2 corresponding to positions 91-99 was solved to 1.8 A resolution. Mutual comparisons of these two structures with structures from other HLA supertypes define and explain the specificity of the P2 and P9 peptide anchor preferences in the B62 HLA supertype. The P2 peptide residue binds to the B-pocket in HLA-B*1501. This pocket is relatively large because of the small Ser67 residue located at the bottom. The peptide proximal part of the B-pocket is hydrophobic, which is consistent with P2 anchor residue preference for Leu. The specificity of the B-pocket is determined by the Met45, Ile66 and Ser67 residues. The apex of the B-pocket is hydrophilic because of the Ser67 residue. The P9 peptide residue binds to the F-pocket in HLA-B*1501. The residues most important for the specificity of this pocket are Tyr74, Leu81, Leu95, Tyr123 and Trp147. These residues create a hydrophobic interior in the F-pocket and their spatial arrangement makes the pocket capable of containing large, bulky peptide side chains. Ser116 is located at the bottom of the F-pocket and makes the bottom of this pocket hydrophilic. Ser116, may act as a hydrogen-bonding partner and as such is a perfect place for binding of a Tyr9 peptide residue. Thus, based on structure information it is now possible to explain the peptide sequence specificity of HLA-B*1501 as previously determined by peptide binding and pool sequencing experiments.

Crystal structures of two peptide-HLA-B*1501 complexes; structural characterization of the HLA-B62 supertype.,Roder G, Blicher T, Justesen S, Johannesen B, Kristensen O, Kastrup J, Buus S, Gajhede M Acta Crystallogr D Biol Crystallogr. 2006 Nov;62(Pt 11):1300-10. Epub 2006, Oct 18. PMID:17057332^[17]

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
↑ Takeuchi T, Iwahara S, Saeki Y, Sasajima H, Yokosawa H. Link between the ubiquitin conjugation system and the ISG15 conjugation system: ISG15 conjugation to the UbcH6 ubiquitin E2 enzyme. J Biochem. 2005 Dec;138(6):711-9. PMID:16428300 doi:10.1093/jb/mvi172
↑ David Y, Ziv T, Admon A, Navon A. The E2 ubiquitin conjugating enzymes direct polyubiquitination to preferred lysines. J Biol Chem. 2010 Jan 8. PMID:20061386 doi:M109.089003
↑ Roder G, Blicher T, Justesen S, Johannesen B, Kristensen O, Kastrup J, Buus S, Gajhede M. Crystal structures of two peptide-HLA-B*1501 complexes; structural characterization of the HLA-B62 supertype. Acta Crystallogr D Biol Crystallogr. 2006 Nov;62(Pt 11):1300-10. Epub 2006, Oct 18. PMID:17057332 doi:10.1107/S0907444906027636

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/1xr9"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1xr9]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XR9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1XR9 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=URE:UREA'>URE</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=URE:UREA'>URE</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1xr8|1xr8]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1xr8|1xr8]]</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HLA-Bw62.1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), B2M ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HLA-Bw62.1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), B2M ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] </span></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xr9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xr9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1xr9 RCSB], [http://www.ebi.ac.uk/pdbsum/1xr9 PDBsum]</span></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=1xr9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xr9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1xr9 RCSB], [http://www.ebi.ac.uk/pdbsum/1xr9 PDBsum]</span></td></tr>
-<table>
+</table>
 == Disease ==
 [[http://www.uniprot.org/uniprot/1B15_HUMAN 1B15_HUMAN]] Defects in HLA-B are a cause of susceptibility to Stevens-Johnson syndrome (SJS) [MIM:[http://omim.org/entry/608579 608579]]. A rare blistering mucocutaneous disease that share clinical and histopathologic features with toxic epidermal necrolysis. Both disorders are characterized by high fever, malaise, and a rapidly developing blistering exanthema of macules and target-like lesions accompanied by mucosal involvement. Stevens-Johnson syndrome is a milder disease characterized by destruction and detachment of the skin epithelium and mucous membranes involving less than 10% of the body surface area. Ocular symptoms include ulcerative conjunctivitis, keratitis, iritis, uveitis and sometimes blindness. It can be caused by a severe adverse reaction to particular types of medication, although Mycoplasma infections may induce some cases. Note=Allele B*15:02 is associated with susceptibility to Stevens-Johnson syndrome. [[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>
@@ Line 41: / Line 41: @@
 [[Category: Homo sapiens]]
 [[Category: Ubiquitin--protein ligase]]
-[[Category: Blicher, T.]]
+[[Category: Blicher, T]]
-[[Category: Buus, S.]]
+[[Category: Buus, S]]
-[[Category: Gajhede, M.]]
+[[Category: Gajhede, M]]
-[[Category: Johannessen, B R.]]
+[[Category: Johannessen, B R]]
-[[Category: Kristensen, O.]]
+[[Category: Kristensen, O]]
-[[Category: Roder, G.]]
+[[Category: Roder, G]]
 [[Category: Hla]]
 [[Category: Hla-b*1501]]

1xr9

From Proteopedia

Revision as of 08:49, 8 January 2015

Crystal Structures of HLA-B*1501 in Complex with Peptides from Human UbcH6 and Epstein-Barr Virus EBNA-3

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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