| Structural highlights
2x89 is a 7 chain structure with sequence from Arabian camel and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | 1uqs, 1bd2, 2esv, 2xks, 2ak4, 1ypz, 1im3, 1i7u, 1uxw, 1c16, 1hsa, 2axf, 1gzp, 2bnq, 1w72, 2jcc, 2bck, 1de4, 2vlk, 1exu, 1qrn, 2hla, 1mhe, 1eez, 1im9, 1jht, 1qqd, 1qr1, 1zs8, 1hla, 1jgd, 1i1y, 1vgk, 1age, 1ur7, 1s9x, 1hhg, 2x4u, 1duz, 1a9e, 2clr, 3hla, 1m05, 2x4o, 1tvb, 2v2w, 1onq, 2x4p, 2vlr, 2bvo, 1a1n, 1lp9, 1zsd, 1m6o, 1hhk, 1zt4, 1hsb, 1ce6, 2xku, 1x7q, 1py4, 1syv, 2j8u, 2xpg, 1sys, 1ogt, 2x4t, 1cg9, 1p7q, 1q94, 1jnj, 1agb, 2d31, 1xz0, 1lds, 1hhh, 1tvh, 1xr8, 2bss, 1a1m, 1e28, 2bvp, 2v2x, 1xr9, 2gj6, 2x4r, 1qlf, 1efx, 1tmc, 2av1, 1qsf, 1kpr, 1duy, 1jge, 2hjl, 1qew, 1w0v, 1k5n, 1ao7, 2bnr, 1xh3, 2bst, 1mi5, 2h26, 1s9y, 1a1o, 2a83, 1agf, 1oga, 2f8o, 2x70, 2cii, 1i7r, 1jf1, 2c7u, 1e27, 2f74, 1w0w, 1gzq, 1uxs, 1akj, 2hjk, 2vb5, 1agd, 2x4n, 1r3h, 1eey, 1i7t, 1ydp, 1i4f, 2vll, 2bsr, 2vlj, 1b0g, 2x4s, 1b0r, 1of2, 1hhi, 1qse, 1a9b, 2axg, 2bvq, 1agc, 1qvo, 1hhj, 1s9w, 1ktl, 1a6z, 2cik, 1i1f, 2uwe, 2av7 |
| 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
Atomic-level structural investigation of the key conformational intermediates of amyloidogenesis remains a challenge. Here we demonstrate the utility of nanobodies to trap and characterize intermediates of beta2-microglobulin (beta2m) amyloidogenesis by X-ray crystallography. For this purpose, we selected five single domain antibodies that block the fibrillogenesis of a proteolytic amyloidogenic fragment of beta2m (DeltaN6beta2m). The crystal structure of DeltaN6beta2m in complex with one of these nanobodies (Nb24) identifies domain swapping as a plausible mechanism of self-association of this amyloidogenic protein. In the swapped dimer, two extended hinge loops-corresponding to the heptapetide NHVTLSQ that forms amyloid in isolation-are unmasked and fold into a new two-stranded antiparallel beta-sheet. The beta-strands of this sheet are prone to self-associate and stack perpendicular to the direction of the strands to build large intermolecular beta-sheets that run parallel to the axis of growing oligomers, providing an elongation mechanism by self-templated growth.
Atomic structure of a nanobody-trapped domain-swapped dimer of an amyloidogenic {beta}2-microglobulin variant.,Domanska K, Vanderhaegen S, Srinivasan V, Pardon E, Dupeux F, Marquez JA, Giorgetti S, Stoppini M, Wyns L, Bellotti V, Steyaert J Proc Natl Acad Sci U S A. 2011 Jan 10. PMID:21220305[15]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Domanska K, Vanderhaegen S, Srinivasan V, Pardon E, Dupeux F, Marquez JA, Giorgetti S, Stoppini M, Wyns L, Bellotti V, Steyaert J. Atomic structure of a nanobody-trapped domain-swapped dimer of an amyloidogenic {beta}2-microglobulin variant. Proc Natl Acad Sci U S A. 2011 Jan 10. PMID:21220305 doi:10.1073/pnas.1008560108
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