beta 2 microglobulin

Summary

Summary: An 11-kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants.

Top Publications

  1. Eakin C, Miranker A. From chance to frequent encounters: origins of beta2-microglobulin fibrillogenesis. Biochim Biophys Acta. 2005;1753:92-9 pubmed
    ..We assert that beta2m amyloid fiber formation at neutral pH may be facilitated by rearrangements catalyzed by the transient and pair wise tethering of beta2m at the blood/dialysate interface present during therapeutic hemodialysis. ..
  2. Platt G, Routledge K, Homans S, Radford S. Fibril growth kinetics reveal a region of beta2-microglobulin important for nucleation and elongation of aggregation. J Mol Biol. 2008;378:251-63 pubmed publisher
  3. Platt G, Radford S. Glimpses of the molecular mechanisms of beta2-microglobulin fibril formation in vitro: aggregation on a complex energy landscape. FEBS Lett. 2009;583:2623-9 pubmed publisher
  4. 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;380:543-7 pubmed publisher
    ..8A resolution. The W60V mutant structural features are discussed, focusing on the roles of the DE loop and of residue 60 in relation to ?2m structure and its amyloid aggregation trends. ..
  5. Calabrese M, Eakin C, Wang J, Miranker A. A regulatable switch mediates self-association in an immunoglobulin fold. Nat Struct Mol Biol. 2008;15:965-71 pubmed
    ..The consequences of this isomerization are evident and reveal a molecular basis for the conversion of this robust monomeric protein into an amyloid-competent state. ..
  6. Xue W, Homans S, Radford S. Systematic analysis of nucleation-dependent polymerization reveals new insights into the mechanism of amyloid self-assembly. Proc Natl Acad Sci U S A. 2008;105:8926-31 pubmed publisher
  7. 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
  8. White H, Hodgkinson J, Jahn T, Cohen Krausz S, Gosal W, Müller S, et al. Globular tetramers of beta(2)-microglobulin assemble into elaborate amyloid fibrils. J Mol Biol. 2009;389:48-57 pubmed publisher
    ..These findings suggest a more complex superstructure for amyloid than hitherto suspected and prompt a re-evaluation of the defining features of the amyloid fold. ..
  9. Fabian H, Gast K, Laue M, Misselwitz R, Uchanska Ziegler B, Ziegler A, et al. Early stages of misfolding and association of beta2-microglobulin: insights from infrared spectroscopy and dynamic light scattering. Biochemistry. 2008;47:6895-906 pubmed publisher

More Information

Publications62

  1. Menaa C, Esser E, Sprague S. Beta2-microglobulin stimulates osteoclast formation. Kidney Int. 2008;73:1275-81 pubmed publisher
    ..These results show that beta(2)M stimulates osteoclastogenesis, supporting its direct role in causing bone destruction in patients with CKD. ..
  2. Antwi K, Mahar M, Srikanth R, Olbris M, Tyson J, Vachet R. Cu(II) organizes beta-2-microglobulin oligomers but is released upon amyloid formation. Protein Sci. 2008;17:748-59 pubmed publisher
    ..Thus, Cu(II) appears to play a catalytic role by enabling the organization of the necessary oligomeric intermediates that precede beta2m amyloid formation. ..
  3. Yamamoto K, Yagi H, Ozawa D, Sasahara K, Naiki H, Goto Y. Thiol compounds inhibit the formation of amyloid fibrils by beta 2-microglobulin at neutral pH. J Mol Biol. 2008;376:258-68 pubmed
    ..The results suggest that reductants such as cysteine and dithiothreitol would be useful for preventing the formation of beta2-m amyloid fibrils under physiological conditions. ..
  4. Sasahara K, Yagi H, Sakai M, Naiki H, Goto Y. Amyloid nucleation triggered by agitation of beta2-microglobulin under acidic and neutral pH conditions. Biochemistry. 2008;47:2650-60 pubmed publisher
  5. 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. ..
  6. 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. ..
  7. Relini A, De Stefano S, Torrassa S, Cavalleri O, Rolandi R, Gliozzi A, et al. Heparin strongly enhances the formation of beta2-microglobulin amyloid fibrils in the presence of type I collagen. J Biol Chem. 2008;283:4912-20 pubmed
    ..The formation of this beta2-m species, which has a strong propensity to aggregate, might play an important role in the acceleration of local amyloid deposition. ..
  8. 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. ..
  9. 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. ..
  10. Corlin D, Johnsen C, Nissen M, Heegaard N. A beta2-microglobulin cleavage variant fibrillates at near-physiological pH. Biochem Biophys Res Commun. 2009;381:187-91 pubmed publisher
    ..This may explain the apparent lack of detectable amounts of the variant beta2m in extracts of amyloid from DRA patients. ..
  11. Eichner T, Radford S. A generic mechanism of beta2-microglobulin amyloid assembly at neutral pH involving a specific proline switch. J Mol Biol. 2009;386:1312-26 pubmed
    ..In this mechanism, amyloid formation is initiated by a specific cis to trans proline switch, the rate of which we show to be controlled by the amino acid sequence proximal to P32 and to the applied solution conditions. ..
  12. Tarakanova V, Suarez F, Tibbetts S, Jacoby M, Weck K, Hess J, et al. Murine gammaherpesvirus 68 infection is associated with lymphoproliferative disease and lymphoma in BALB beta2 microglobulin-deficient mice. J Virol. 2005;79:14668-79 pubmed
    ..Our findings suggest that gammaHV68 induces lymphomas via hit-and-run oncogenesis, paracrine effects, or stimulation of chronic inflammation. ..
  13. Linse S, Cabaleiro Lago C, Xue W, Lynch I, Lindman S, Thulin E, et al. Nucleation of protein fibrillation by nanoparticles. Proc Natl Acad Sci U S A. 2007;104:8691-6 pubmed
    ..It also opens the door to new routes for the controlled self-assembly of proteins and peptides into novel nanomaterials. ..
  14. Paduraru C, Spiridon L, Yuan W, Bricard G, Valencia X, Porcelli S, et al. An N-linked glycan modulates the interaction between the CD1d heavy chain and beta 2-microglobulin. J Biol Chem. 2006;281:40369-78 pubmed
    ..Modeling the glycans on the published structure indicated that glycan 2 interacts significantly with both the CD1d heavy chain and beta(2)m, which may explain these unusual properties. ..
  15. Evenepoel P, Bammens B, Verbeke K, Vanrenterghem Y. Superior dialytic clearance of beta(2)-microglobulin and p-cresol by high-flux hemodialysis as compared to peritoneal dialysis. Kidney Int. 2006;70:794-9 pubmed
    ..In conclusion, superior dialytic clearance of both water-soluble solutes, beta(2)M, and pcr is achieved by high-flux HD as compared to PD. ..
  16. Myers S, Thomson N, Radford S, Ashcroft A. Investigating the structural properties of amyloid-like fibrils formed in vitro from beta2-microglobulin using limited proteolysis and electrospray ionisation mass spectrometry. Rapid Commun Mass Spectrom. 2006;20:1628-36 pubmed
    ..The data demonstrate that the organisation of the polypeptide chain in fibrils with different morphological features differs considerably, despite the fact that the fibrils possess a common cross-beta architecture. ..
  17. Sánchez de Groot N, Pallares I, Aviles F, Vendrell J, Ventura S. Prediction of "hot spots" of aggregation in disease-linked polypeptides. BMC Struct Biol. 2005;5:18 pubmed
    ..The proposed method might become a useful tool for the future development of sequence-targeted anti-aggregation pharmaceuticals. ..
  18. Mimmi M, Jørgensen T, Pettirossi F, Corazza A, Viglino P, Esposito G, et al. Variants of beta-microglobulin cleaved at lysine-58 retain the main conformational features of the native protein but are more conformationally heterogeneous and unstable at physiological temperature. FEBS J. 2006;273:2461-74 pubmed
    ..The instability and conformational heterogeneity of this variant suggest its involvement in beta2-microglobulin amyloidogenicity in vivo. ..
  19. Chen Y, Dokholyan N. A single disulfide bond differentiates aggregation pathways of beta2-microglobulin. J Mol Biol. 2005;354:473-82 pubmed
    ..We propose that the propagation of domain swapping is the aggregation mechanism for the oxidized beta2m, while "parallel stacking" of partially unfolded beta2m is the aggregation mechanism for the reduced beta2m. ..
  20. 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. ..
  21. Nomura T, Huang W, Zhau H, Wu D, Xie Z, Mimata H, et al. Beta2-microglobulin promotes the growth of human renal cell carcinoma through the activation of the protein kinase A, cyclic AMP-responsive element-binding protein, and vascular endothelial growth factor axis. Clin Cancer Res. 2006;12:7294-305 pubmed
    ..Our results showed for the first time that the beta2M-protein kinase A-CREB-VEGF signaling axis plays a crucial role in support of renal cell carcinoma growth and progression and reveals a novel therapeutic target. ..
  22. Bianchini M, Levy E, Zucchini C, Pinski V, Macagno C, De Sanctis P, et al. Comparative study of gene expression by cDNA microarray in human colorectal cancer tissues and normal mucosa. Int J Oncol. 2006;29:83-94 pubmed
    ..These genes are involved in pathways not previously implicated in CRC pathogenesis and they may provide new targets for therapy. ..
  23. 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. ..
  24. 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. ..
  25. Margalit A, Sheikhet H, Carmi Y, Berko D, Tzehoval E, Eisenbach L, et al. Induction of antitumor immunity by CTL epitopes genetically linked to membrane-anchored beta2-microglobulin. J Immunol. 2006;176:217-24 pubmed
    ..Our results highlight the immunotherapeutic potential of membranal beta2m as a universal scaffold for optimizing Ag presentation by MHC-I molecules. ..
  26. Stoppini M, Mangione P, Monti M, Giorgetti S, Marchese L, Arcidiaco P, et al. Proteomics of beta2-microglobulin amyloid fibrils. Biochim Biophys Acta. 2005;1753:23-33 pubmed
    ..Other previously reported chemical modifications cannot be excluded, but should involve less than 1-2% of the intact molecule. ..
  27. Ivanova M, Thompson M, Eisenberg D. A systematic screen of beta(2)-microglobulin and insulin for amyloid-like segments. Proc Natl Acad Sci U S A. 2006;103:4079-82 pubmed
  28. Ward R, Greene T, Hartmann B, Samtleben W. Resistance to intercompartmental mass transfer limits beta2-microglobulin removal by post-dilution hemodiafiltration. Kidney Int. 2006;69:1431-7 pubmed
    ..This finding suggests that alternative strategies, such as increased treatment times or frequency of treatment, are needed to further reduce plasma beta(2)-microglobulin concentrations. ..
  29. Borysik A, Morten I, Radford S, Hewitt E. Specific glycosaminoglycans promote unseeded amyloid formation from beta2-microglobulin under physiological conditions. Kidney Int. 2007;72:174-81 pubmed
    ..This leads to the accumulation of beta2m in fibrillar deposits. Our data rationalize the joint-specific deposition of beta2m amyloid in DRA, suggesting mechanisms by which amyloid formation may be promoted. ..
  30. Manolova V, Kistowska M, Paoletti S, Baltariu G, Bausinger H, Hanau D, et al. Functional CD1a is stabilized by exogenous lipids. Eur J Immunol. 2006;36:1083-92 pubmed
    ..These results indicate a functional dichotomy between CD1a and CD1b molecules and provide new information on how the lipid antigenic repertoire is immunologically sampled. ..
  31. Relini A, Canale C, De Stefano S, Rolandi R, Giorgetti S, Stoppini M, et al. Collagen plays an active role in the aggregation of beta2-microglobulin under physiopathological conditions of dialysis-related amyloidosis. J Biol Chem. 2006;281:16521-9 pubmed
  32. Huang W, Wu D, Xie Z, Zhau H, Nomura T, Zayzafoon M, et al. beta2-microglobulin is a signaling and growth-promoting factor for human prostate cancer bone metastasis. Cancer Res. 2006;66:9108-16 pubmed
    ..These results suggest that beta2M signaling is an attractive new therapeutic target for the treatment of lethal prostate cancer bone metastasis. ..
  33. Kardos J, Okuno D, Kawai T, Hagihara Y, Yumoto N, Kitagawa T, et al. Structural studies reveal that the diverse morphology of beta(2)-microglobulin aggregates is a reflection of different molecular architectures. Biochim Biophys Acta. 2005;1753:108-20 pubmed
    ..Extent of the core buried from the solvent in the various states was investigated by H/D exchange of the amide protons. ..
  34. Monti M, Amoresano A, Giorgetti S, Bellotti V, Pucci P. Limited proteolysis in the investigation of beta2-microglobulin amyloidogenic and fibrillar states. Biochim Biophys Acta. 2005;1753:44-50 pubmed
    ..On the basis of these results, a molecular mechanism for fibril formation has been proposed. ..
  35. 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
  36. Eakin C, Berman A, Miranker A. A native to amyloidogenic transition regulated by a backbone trigger. Nat Struct Mol Biol. 2006;13:202-8 pubmed
    ..Furthermore, it is stable and folded, enabling us to unambiguously determine the initiating conformational changes for amyloid assembly at atomic resolution. ..
  37. Herrero Morín J, Málaga S, Fernandez N, Rey C, Dieguez M, Solis G, et al. Cystatin C and beta2-microglobulin: markers of glomerular filtration in critically ill children. Crit Care. 2007;11:R59 pubmed
    ..792 for cystatin C, 0.802 and 0.799 for B2M, and 0.633 and 0.625 for creatinine). Serum cystatin C and B2M were confirmed as easy and useful markers, better than serum creatinine, to detect acute kidney injury in critically ill children. ..
  38. Calabrese M, Miranker A. Formation of a stable oligomer of beta-2 microglobulin requires only transient encounter with Cu(II). J Mol Biol. 2007;367:1-7 pubmed
    ..Our results are consistent with our hypothesis that transient encounter of full-length wild-type beta2m with transition metal cation at the dialysis membrane interface is causal to dialysis related amyloidosis. ..
  39. Giorgetti S, Stoppini M, Tennent G, Relini A, Marchese L, Raimondi S, et al. Lysine 58-cleaved beta2-microglobulin is not detectable by 2D electrophoresis in ex vivo amyloid fibrils of two patients affected by dialysis-related amyloidosis. Protein Sci. 2007;16:343-9 pubmed
    ..In contrast, we found no evidence for the presence of DeltaK58-beta2m. ..
  40. Dobson C. An accidental breach of a protein's natural defenses. Nat Struct Mol Biol. 2006;13:295-7 pubmed
  41. Yamaguchi K, Naiki H, Goto Y. Mechanism by which the amyloid-like fibrils of a beta 2-microglobulin fragment are induced by fluorine-substituted alcohols. J Mol Biol. 2006;363:279-88 pubmed
    ..e. H-bonds) in and between peptides leads to the formation of ordered fibrils with a bell-shaped concentration dependence...
  42. 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. ..
  43. Yamagami T, Suna T, Fukui Y, Ohashi F, Takada S, Sakurai H, et al. Biological variations in cadmium, alpha 1-microglobulin, beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase in adult women in a non-polluted area. Int Arch Occup Environ Health. 2008;81:263-71 pubmed
    ..Very low within-subject variation in Cd-B may suggest the advantage of Cd-B over Cd-U for individual evaluation among general populations if blood sampling is accepted. ..
  44. Al Sobhi E, Osoba A, Karar A, Zuraiki A. Multiple myeloma of the central nervous system: a clinicopathological review. East Mediterr Health J. 2009;15:1570-9 pubmed
    ..We review this here along with our clinicopathological experience and a summary of our present knowledge of this condition. ..
  45. Meng F, Shen C, He Y, Miao F, Zhang J. Cloning and expression of three peptide-linked beta2-microglobulin molecules in Escherichia coli with an isocaudamer technique. Biotechnol Lett. 2009;31:831-6 pubmed publisher
    ..This strategy facilitates the construction of peptide-linked beta2m molecules and will simplify the preparation of major histocompatibility complex-peptide complexes. ..
  46. Magdo H, Forman J, Graber N, Newman B, Klein K, Satlin L, et al. Grand rounds: nephrotoxicity in a young child exposed to uranium from contaminated well water. Environ Health Perspect. 2007;115:1237-41 pubmed
  47. Chu Q, Wang L, Liu G. [Clinical observation on acupuncture for treatment of diabetic nephropathy]. Zhongguo Zhen Jiu. 2007;27:488-90 pubmed
    ..Acupuncture can improve lipid metabolism and protect the renal function of the patient with early metaphase diabetes. ..
  48. Wierda W, O Brien S, Wang X, Faderl S, Ferrajoli A, Do K, et al. Characteristics associated with important clinical end points in patients with chronic lymphocytic leukemia at initial treatment. J Clin Oncol. 2009;27:1637-43 pubmed publisher
    ..Treatment had an impact on the significance of these factors. Prognostic models may help patients and clinicians in decision making as well as facilitate clinical research through design and analyses of clinical trials. ..
  49. Tanida E, Usuda K, Kono K, Kawano A, Tsuji H, Imanishi M, et al. Urinary scandium as predictor of exposure: effects of scandium chloride hexahydrate on renal function in rats. Biol Trace Elem Res. 2009;130:273-82 pubmed publisher
    ..We propose that the analytical method and results described in this study will be of great importance for future toxicological studies on Sc exposure...
  50. Sugden K, Pariante C, McGuffin P, Aitchison K, D Souza U. Housekeeping gene expression is affected by antidepressant treatment in a mouse fibroblast cell line. J Psychopharmacol. 2010;24:1253-9 pubmed publisher
    ..In conclusion, care must be taken when choosing reference transcripts for analysis in qPCR. For in-vitro pharmacological studies, it should not be assumed that 'housekeeping' genes are stable. ..
  51. Sahsivar M, Narin C, Kiyici A, Toy H, Ege E, Sarigul A. The effect of iloprost on renal dysfunction after renal I/R using cystatin C and beta2-microglobulin monitoring. Shock. 2009;32:498-502 pubmed publisher
    ..In contrast, we have shown that there are no significant changes in the levels of serum B2M levels that would make it an accurate diagnostic tool for detecting acute changes in renal injury subject to renal I/R in rats. ..
  52. Townsend A, Ohlen C, Bastin J, Ljunggren H, Foster L, Kärre K. Pillars article: Association of class I major histocompatibility heavy and light chains induced by viral peptides. Nature 1989. 340: 443-448. J Immunol. 2007;179:4301-6 pubmed
  53. Garcia Manero G, Shan J, Faderl S, Cortes J, Ravandi F, Borthakur G, et al. A prognostic score for patients with lower risk myelodysplastic syndrome. Leukemia. 2008;22:538-43 pubmed
    ..2 months (95% CI 13-18). In summary, this analysis indicates that it is possible to identify patients with lower risk MDS and poor prognosis who may benefit from early intervention. ..