Genomes and Genes
Gene Symbol: B2M
Alias: IMD43, beta-2-microglobulin, beta chain of MHC class I molecules, beta-2-microglobin
- Iwata K, Fujiwara T, Matsuki Y, Akutsu H, Takahashi S, Naiki H, et al. 3D structure of amyloid protofilaments of beta2-microglobulin fragment probed by solid-state NMR. Proc Natl Acad Sci U S A. 2006;103:18119-24 pubmed..By revealing the structure of beta(2)-microglobulin protofilament-like fibrils, this work represents technical progress in analyzing amyloid fibrils in general through solid-state NMR. ..
- Jones S, Manning J, Kad N, Radford S. Amyloid-forming peptides from beta2-microglobulin-Insights into the mechanism of fibril formation in vitro. J Mol Biol. 2003;325:249-57 pubmed
- Ladner C, Chen M, Smith D, Platt G, Radford S, Langen R. Stacked sets of parallel, in-register beta-strands of beta2-microglobulin in amyloid fibrils revealed by site-directed spin labeling and chemical labeling. J Biol Chem. 2010;285:17137-47 pubmed publisher..The results suggest an organization more complex than the accordion-like beta-sandwich structure commonly proposed for amyloid fibrils. ..
- Jahn T, Parker M, Homans S, Radford S. Amyloid formation under physiological conditions proceeds via a native-like folding intermediate. Nat Struct Mol Biol. 2006;13:195-201 pubmed..The results demonstrate that aggregation pathways can involve self-assembly of highly native-like folding intermediates, and have implications for the prevention of this, and other, amyloid disorders. ..
- Verdone G, Corazza A, Viglino P, Pettirossi F, Giorgetti S, Mangione P, et al. The solution structure of human beta2-microglobulin reveals the prodromes of its amyloid transition. Protein Sci. 2002;11:487-99 pubmed
- Gussow D, Rein R, Ginjaar I, Hochstenbach F, Seemann G, Kottman A, et al. The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit. J Immunol. 1987;139:3132-8 pubmedThe human genomic clone pb2m13 contains a functional beta 2-microglobulin (B2m) gene, which upon transfection is readily expressed in murine fibroblasts...
- Yanagi K, Sakurai K, Yoshimura Y, Konuma T, Lee Y, Sugase K, et al. The monomer-seed interaction mechanism in the formation of the ?2-microglobulin amyloid fibril clarified by solution NMR techniques. J Mol Biol. 2012;422:390-402 pubmed publisher..Our results provide general information about the extension of amyloid fibrils. ..
- Myers S, Jones S, Jahn T, Morten I, Tennent G, Hewitt E, et al. A systematic study of the effect of physiological factors on beta2-microglobulin amyloid formation at neutral pH. Biochemistry. 2006;45:2311-21 pubmed
- Ricagno S, Colombo M, de Rosa M, Sangiovanni E, Giorgetti S, Raimondi S, et al. DE loop mutations affect beta2-microglobulin stability and amyloid aggregation. Biochem Biophys Res Commun. 2008;377:146-50 pubmed publisher..The experimental evidences gathered on the two mutants reinforce the hypothesis that conformational strain in the DE loop can affect beta2m stability and amyloid aggregation properties. ..
- Huang W, Havel J, Zhau H, Qian W, Lue H, Chu C, et al. Beta2-microglobulin signaling blockade inhibited androgen receptor axis and caused apoptosis in human prostate cancer cells. Clin Cancer Res. 2008;14:5341-7 pubmed publisher..The beta2M antibody is a novel and promising therapeutic agent for the treatment of human prostate cancers. ..
- Federico M, Guglielmi C, Luminari S, Mammi C, Marcheselli L, Gianelli U, et al. Prognostic relevance of serum beta2 microglobulin in patients with follicular lymphoma treated with anthracycline-containing regimens. A GISL study. Haematologica. 2007;92:1482-8 pubmed..We thus suggest that beta2M be routinely assessed and tested in future prognostic studies of FL patients treated with combination chemotherapy and anti-CD20 agents. ..
- Mangione P, Esposito G, Relini A, Raimondi S, Porcari R, Giorgetti S, et al. Structure, folding dynamics, and amyloidogenesis of D76N β2-microglobulin: roles of shear flow, hydrophobic surfaces, and α-crystallin. J Biol Chem. 2013;288:30917-30 pubmed publisher..Elucidation of this crucial causative event in clinical amyloidosis should also help to explain the hitherto mysterious timing and location of amyloid deposition. ..
- Debelouchina G, Platt G, Bayro M, Radford S, Griffin R. Magic angle spinning NMR analysis of beta2-microglobulin amyloid fibrils in two distinct morphologies. J Am Chem Soc. 2010;132:10414-23 pubmed publisher..Our results suggest that the distinct macroscopic morphological features observed for the two types of fibrils result from variations in structure and dynamics at the molecular level. ..
- 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;142:413-9 pubmed..We consider that the enhanced fibrillation is more directly coupled with the decreased stability leading to the increased propensity of exposing amyloidogenic regions. ..
- Sasahara K, Yagi H, Naiki H, Goto Y. Heat-induced conversion of beta(2)-microglobulin and hen egg-white lysozyme into amyloid fibrils. J Mol Biol. 2007;372:981-91 pubmed
- Jahn T, Tennent G, Radford S. A common beta-sheet architecture underlies in vitro and in vivo beta2-microglobulin amyloid fibrils. J Biol Chem. 2008;283:17279-86 pubmed publisher..Our results endorse the relevance of biophysical studies for the investigation of the molecular mechanisms of beta(2)-microglobulin fibrillogenesis, knowledge about which may inform understanding of the pathobiology of this protein. ..
- Valleix S, Gillmore J, Bridoux F, Mangione P, Dogan A, Nedelec B, et al. Hereditary systemic amyloidosis due to Asp76Asn variant ?2-microglobulin. N Engl J Med. 2012;366:2276-83 pubmed publisher..Comprehensive biophysical characterization of the ?(2)-microglobulin variant, including its 1.40-Å, three-dimensional structure, should allow further elucidation of fibrillogenesis and protein misfolding. ..
- Mendoza V, Antwi K, Barón Rodríguez M, Blanco C, Vachet R. Structure of the preamyloid dimer of beta-2-microglobulin from covalent labeling and mass spectrometry. Biochemistry. 2010;49:1522-32 pubmed publisher..In addition, our data clearly indicate that a dimer interface involving the interactions of D-D strands from separate protein units as seen in the recent crystal structures of two mutant beta2m oligomers is unlikely. ..
- Giorgetti S, Raimondi S, Pagano K, Relini A, Bucciantini M, Corazza A, et al. Effect of tetracyclines on the dynamics of formation and destructuration of beta2-microglobulin amyloid fibrils. J Biol Chem. 2011;286:2121-31 pubmed publisher..In these tissues, the doxycycline concentration reaches values several folds higher than those resulting in inhibition of amyloidogenesis and amyloid destructuration in vitro. ..
- Kloor M, Michel S, Buckowitz B, Ruschoff J, Buttner R, Holinski Feder E, et al. Beta2-microglobulin mutations in microsatellite unstable colorectal tumors. Int J Cancer. 2007;121:454-8 pubmed..However, no beta2m mutations were observed in metastasized CRCs (UICC stage IV, p=0.04). These results suggest that functional beta2m may be necessary for distant metastasis formation in CRC patients. ..
- Kihara M, Chatani E, Iwata K, Yamamoto K, Matsuura T, Nakagawa A, et al. Conformation of amyloid fibrils of beta2-microglobulin probed by tryptophan mutagenesis. J Biol Chem. 2006;281:31061-9 pubmed..In addition, the fluorescence spectra of fibrils prepared at pH 2.5 and 7.0 revealed a large difference in the fluorescence intensity for W60-beta2-m, implying a major structural difference between them. ..
- Gosal W, Morten I, Hewitt E, Smith D, Thomson N, Radford S. Competing pathways determine fibril morphology in the self-assembly of beta2-microglobulin into amyloid. J Mol Biol. 2005;351:850-64 pubmed
- Kad N, Thomson N, Smith D, Smith D, Radford S. Beta(2)-microglobulin and its deamidated variant, N17D form amyloid fibrils with a range of morphologies in vitro. J Mol Biol. 2001;313:559-71 pubmed..Using kinetic experiments we suggest that the immature fibrils observed previously do not represent intermediates in the assembly of fully mature amyloid, at least under the conditions studied here. ..
- Hong D, Gozu M, Hasegawa K, Naiki H, Goto Y. Conformation of beta 2-microglobulin amyloid fibrils analyzed by reduction of the disulfide bond. J Biol Chem. 2002;277:21554-60 pubmed..Taken together, the disulfide bond once exposed to the solvent upon acid denaturation may be progressively buried in the interior of the amyloid fibrils during its formation. ..
- Paschen A, Méndez R, Jimenez P, Sucker A, Ruiz Cabello F, Song M, et al. Complete loss of HLA class I antigen expression on melanoma cells: a result of successive mutational events. Int J Cancer. 2003;103:759-67 pubmed..Antigen presentation was not inducible with IFN-gamma but could be restored after transfection of tumor cells with b2m cDNA, indicating a defect in b2m expression...
- Nomura T, Huang W, Seo S, Zhau H, Mimata H, Chung L. Targeting beta2-microglobulin mediated signaling as a novel therapeutic approach for human renal cell carcinoma. J Urol. 2007;178:292-300 pubmed
- Juraschek S, Coresh J, Inker L, Levey A, Kottgen A, Foster M, et al. Comparison of serum concentrations of ?-trace protein, ?2-microglobulin, cystatin C, and creatinine in the US population. Clin J Am Soc Nephrol. 2013;8:584-92 pubmed publisher..Future studies should examine these markers with measured GFR to determine their diagnostic and prognostic utility. ..
- Gattoni Celli S, Kirsch K, Timpane R, Isselbacher K. Beta 2-microglobulin gene is mutated in a human colon cancer cell line (HCT) deficient in the expression of HLA class I antigens on the cell surface. Cancer Res. 1992;52:1201-4 pubmed..Therefore, it would appear that in HCT cells the beta 2m genes have undergone two different mutational changes. This is the first molecular demonstration of beta 2m mutations in a human epithelial cell line. ..
- Saper M, Bjorkman P, Wiley D. Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A resolution. J Mol Biol. 1991;219:277-319 pubmed..A possible role for beta 2m in stabilizing permissible peptide complexes during folding and assembly is presented. ..
- Li Z, Zhu Y, Sun J, Xia Y, Huang J, Zou B, et al. Serum beta2-microglobin is a predictor of prognosis in patients with upper aerodigestive tract NK/T-cell lymphoma. Ann Hematol. 2012;91:1265-70 pubmed publisher..Our study suggested high serum ?2-M was a novel predictor of prognosis in patients with UNKTL. A simply and regular way might be established to identify UNKTL patients of different risks at diagnosis. ..
- McParland V, Kalverda A, Homans S, Radford S. Structural properties of an amyloid precursor of beta(2)-microglobulin. Nat Struct Biol. 2002;9:326-31 pubmed..The data offer a rationale as to why these proteins are both amyloidogenic at low pH and suggest that amyloidosis of these and other proteins may involve ordered assembly from a precursor with similar conformational features. ..
- Chatani E, Kato M, Kawai T, Naiki H, Goto Y. Main-chain dominated amyloid structures demonstrated by the effect of high pressure. J Mol Biol. 2005;352:941-51 pubmed..Moreover, the amyloid structure without optimal packing will enable various isoforms to form, suggesting the structural basis of multiple forms of amyloid fibrils in contrast to the unique native-fold. ..
- Ohhashi Y, Kihara M, Naiki H, Goto Y. Ultrasonication-induced amyloid fibril formation of beta2-microglobulin. J Biol Chem. 2005;280:32843-8 pubmed..5. These results indicate that ultrasonication is one form of agitation triggering the formation of amyloid fibrils of beta2-m, producing fibrils adapted to the respective pH. ..
- Tsimberidou A, Kantarjian H, Wen S, O Brien S, Cortes J, Wierda W, et al. The prognostic significance of serum beta2 microglobulin levels in acute myeloid leukemia and prognostic scores predicting survival: analysis of 1,180 patients. Clin Cancer Res. 2008;14:721-30 pubmed publisher..Serum beta2M levels can help predict outcome in patients > or =60 years with untreated AML, and their use is strongly encouraged. ..
- Ma B, Nussinov R. Molecular dynamics simulations of the unfolding of beta(2)-microglobulin and its variants. Protein Eng. 2003;16:561-75 pubmed..These conformational changes may relate to polymerization tendencies of these variants. ..
- Winchester J, Salsberg J, Levin N. Beta-2 microglobulin in ESRD: an in-depth review. Adv Ren Replace Ther. 2003;10:279-309 pubmed..There seems to be a relative risk reduction in mortality when patients are treated with dialysis membranes that have a higher clearance of beta-2 microglobulin. ..
- Rosano C, Zuccotti S, Mangione P, Giorgetti S, Bellotti V, Pettirossi F, et al. beta2-microglobulin H31Y variant 3D structure highlights the protein natural propensity towards intermolecular aggregation. J Mol Biol. 2004;335:1051-64 pubmed
- Chiba T, Hagihara Y, Higurashi T, Hasegawa K, Naiki H, Goto Y. Amyloid fibril formation in the context of full-length protein: effects of proline mutations on the amyloid fibril formation of beta2-microglobulin. J Biol Chem. 2003;278:47016-24 pubmed..The present results reveal that, in addition, stability of the amyloid fibrils is a key factor determining the amyloidogenic potential of the proteins. ..
- Krangel M, Orr H, Strominger J. Assembly and maturation of HLA-A and HLA-B antigens in vivo. Cell. 1979;18:979-91 pubmed..These observations are discussed in relation to in vivo and in vitro studies on the biosynthesis of a variety of secreted proteins and membrane proteins. ..
- Rennella E, Cutuil T, Schanda P, Ayala I, Gabel F, Forge V, et al. Oligomeric states along the folding pathways of ?2-microglobulin: kinetics, thermodynamics, and structure. J Mol Biol. 2013;425:2722-36 pubmed publisher..This excited state becomes more populated in the transient I-state due to the destabilization of the native conformation by the trans-Pro32 configuration. ..
- Esposito G, Garvey M, Alverdi V, Pettirossi F, Corazza A, Fogolari F, et al. Monitoring the interaction between ?2-microglobulin and the molecular chaperone ?B-crystallin by NMR and mass spectrometry: ?B-crystallin dissociates ?2-microglobulin oligomers. J Biol Chem. 2013;288:17844-58 pubmed publisher..Our findings are highly relevant to the emerging view that molecular chaperone action is intimately involved in the prevention of in vivo amyloid fibril formation. ..
- Okon M, Bray P, Vucelic D. 1H NMR assignments and secondary structure of human beta 2-microglobulin in solution. Biochemistry. 1992;31:8906-15 pubmed..No evidence for any regular helical structure is found. Amide proton-solvent-exchange rate constants and 3JHN alpha coupling constants are evaluated. ..
- Heegaard N, Jørgensen T, Rozlosnik N, Corlin D, Pedersen J, Tempesta A, et al. Unfolding, aggregation, and seeded amyloid formation of lysine-58-cleaved beta 2-microglobulin. Biochemistry. 2005;44:4397-407 pubmed
- Kardos J, Yamamoto K, Hasegawa K, Naiki H, Goto Y. Direct measurement of the thermodynamic parameters of amyloid formation by isothermal titration calorimetry. J Biol Chem. 2004;279:55308-14 pubmed
- Bjorkman P, Saper M, Samraoui B, Bennett W, Strominger J, Wiley D. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987;329:506-12 pubmed..A large groove between the alpha-helices provides a binding site for processed foreign antigens. An unknown 'antigen' is found in this site in crystals of purified HLA-A2. ..
- Hoshino M, Katou H, Hagihara Y, Hasegawa K, Naiki H, Goto Y. Mapping the core of the beta(2)-microglobulin amyloid fibril by H/D exchange. Nat Struct Biol. 2002;9:332-6 pubmed..The present method could be used to obtain residue-specific conformational information of various amyloid fibrils, even though it does not provide a high resolution three-dimensional structure. ..
- Trinh C, Smith D, Kalverda A, Phillips S, Radford S. Crystal structure of monomeric human beta-2-microglobulin reveals clues to its amyloidogenic properties. Proc Natl Acad Sci U S A. 2002;99:9771-6 pubmed
- Katou H, Kanno T, Hoshino M, Hagihara Y, Tanaka H, Kawai T, et al. The role of disulfide bond in the amyloidogenic state of beta(2)-microglobulin studied by heteronuclear NMR. Protein Sci. 2002;11:2218-29 pubmed
- Chen C, Su C, Chien C, Huang C, Chuang H, Fang F, et al. Overexpression of beta2-microglobulin is associated with poor survival in patients with oral cavity squamous cell carcinoma and contributes to oral cancer cell migration and invasion. Br J Cancer. 2008;99:1453-61 pubmed publisher..Taken together, our results suggest that beta2M expression in the tissues is associated with survival and may be involved in tumour progression and metastasis in OCSCC. ..
- Jones S, Smith D, Radford S. Role of the N and C-terminal strands of beta 2-microglobulin in amyloid formation at neutral pH. J Mol Biol. 2003;330:935-41 pubmed..The data are consistent with the view that perturbation of the N and C-terminal edge strands is an important feature in the generation of assembly-competent states of beta(2)m. ..
- Blaho D, Miranker A. Delineating the conformational elements responsible for Cu(2+)-induced oligomerization of beta-2 microglobulin. Biochemistry. 2009;48:6610-7 pubmed publisher..Here, we show that this strong binding affinity need not be directly coupled to oligomerization. We interpret our results in terms of the known structures of beta2m(apo) and a reversible hexameric state of beta2m(holo). ..
- Lee Y, Chatani E, Sasahara K, Naiki H, Goto Y. A comprehensive model for packing and hydration for amyloid fibrils of beta2-microglobulin. J Biol Chem. 2009;284:2169-75 pubmed publisher..These volumetric differences would result from the nature of main-chain-dominated fibrillogenesis. We suggest comprehensive models for these three types of fibrils illustrating packing and hydrational states. ..
- Smith D, Jones S, Serpell L, Sunde M, Radford S. A systematic investigation into the effect of protein destabilisation on beta 2-microglobulin amyloid formation. J Mol Biol. 2003;330:943-54 pubmed..Moreover, we demonstrate that the formation of fibrils with different morphologies in vitro correlates with the relative population of different precursor states. ..
- Colombo M, de Rosa M, Bellotti V, Ricagno S, Bolognesi M. A recurrent D-strand association interface is observed in ?-2 microglobulin oligomers. FEBS J. 2012;279:1131-43 pubmed publisher..Implications for ?2m oligomerization are discussed. ..