4ra3

From Proteopedia

(Difference between revisions)

Revision as of 16:08, 16 November 2017

Crystal structure of dimeric S33C beta-2 microglobulin mutant in complex with Thioflavin (ThT) at 2.8 Angstrom resolution

Structural highlights

4ra3 is a 4 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:	4r9h, 4rah
Gene:	B2M, CDABP0092, HDCMA22P, NM_004048 (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

[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

Early oligomers are crucial in amyloid aggregation; however, due to their transient nature they are among the least structurally characterized species. We focused on the amyloidogenic protein beta2-microglobulin (beta2m) whose early oligomers are still a matter of debate. An intermolecular interaction between D strands of facing beta2m molecules was repeatedly observed, suggesting that such interface may be relevant for beta2m dimerization. In this study, by mutating Ser33 to Cys, and assembling the disulphide-stabilized beta2m homodimer (DimC33), such DD strand interface was locked. Although the isolated DimC33 display a stability similar to wt beta2m under native conditions, it shows enhanced amyloid aggregation propensity. Three distinct crystal structures of DimC33 suggest that dimerization through the DD interface is instrumental for enhancing DimC33 aggregation propensity. Furthermore, the crystal structure of DimC33 in complex with the amyloid-specific dye Thioflavin-T pinpoints a second interface, which likely participates in the first steps of beta2m aggregation. The present data provide new insight into beta2m early steps of amyloid aggregation.

A covalent homodimer probing early oligomers along amyloid aggregation.,Halabelian L, Relini A, Barbiroli A, Penco A, Bolognesi M, Ricagno S Sci Rep. 2015 Sep 30;5:14651. doi: 10.1038/srep14651. PMID:26420657^[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
↑ Halabelian L, Relini A, Barbiroli A, Penco A, Bolognesi M, Ricagno S. A covalent homodimer probing early oligomers along amyloid aggregation. Sci Rep. 2015 Sep 30;5:14651. doi: 10.1038/srep14651. PMID:26420657 doi:http://dx.doi.org/10.1038/srep14651

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/4ra3"

@@ Line 1: / Line 1: @@
 ==Crystal structure of dimeric S33C beta-2 microglobulin mutant in complex with Thioflavin (ThT) at 2.8 Angstrom resolution==
 <StructureSection load='4ra3' size='340' side='right' caption='[[4ra3]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4ra3]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RA3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RA3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4ra3]] is a 4 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=4RA3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RA3 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TFX:2-[4-(DIMETHYLAMINO)PHENYL]-3,6-DIMETHYL-1,3-BENZOTHIAZOL-3-IUM'>TFX</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4r9h|4r9h]], [[4rah|4rah]]</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=4ra3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ra3 OCA], [http://pdbe.org/4ra3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ra3 RCSB], [http://www.ebi.ac.uk/pdbsum/4ra3 PDBsum]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">B2M, CDABP0092, HDCMA22P, NM_004048 ([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=4ra3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ra3 OCA], [http://pdbe.org/4ra3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ra3 RCSB], [http://www.ebi.ac.uk/pdbsum/4ra3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ra3 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 24: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Bolognesi, M]]
 [[Category: Halabelian, L]]

4ra3

From Proteopedia

Revision as of 16:08, 16 November 2017

Crystal structure of dimeric S33C beta-2 microglobulin mutant in complex with Thioflavin (ThT) at 2.8 Angstrom resolution

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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