Beta-2 mikroglobulin
β2 mikroglobulin, znan i kao B2M je komponenta molekula MHC klase I. Molekule MHC-klase imaju α1, α2 i α3 proteine koji su prisutni u svim jedarnim ćelijama (isključujući crvene krvne ćelije).[5][6] Kod ljudi, β2 mikroglobulinskz protein[7] kodiran je genom B2M.[6][8]
Struktura i funkcija
[uredi | uredi izvor]- Aminokiselinska sekvenca
Dužina polipeptidnog lanca je 119 aminokiselina, a molekulska težina 13.715 Da.[9].
10 | 20 | 30 | 40 | 50 | ||||
---|---|---|---|---|---|---|---|---|
MSRSVALAVL | ALLSLSGLEA | IQRTPKIQVY | SRHPAENGKS | NFLNCYVSGF | ||||
HPSDIEVDLL | KNGERIEKVE | HSDLSFSKDW | SFYLLYYTEF | TPTEKDEYAC | ||||
RVNHVTLSQP | KIVKWDRDM |
- Simboli
C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin
β2 microglobulin mikroglobulin leži pored lanca α3 na površini ćelije. Za razliku od α3, β2 nema transmembransku regiju. Neposredno iznad β2 (tj. dalje od ćelije) nalazi se lanac α1, koji je sam pored α2.
β2 mikroglobulin pridružuje se ne samo na alfa lanac molekula MHC klase I, već i na molekule slične klasi I kao što je CD1 (kod ljudi pet gena), glavni kompleks histokompatibilnosti , MR1, neonatusni Fc receptor (FcRn) i Qa-1 (oblik aloantigena). Ipak, gen β2 mikroglobulina nalazi se izvan lokusa MHC (HLA), na drugom hromosomu.
Dodatna funkcija je povezanost sa HFE protein, zajedno regulišući ekspresiju hepcidina u jetri koji cilja transporter gvožđa feroportin na bazolateralnoj membrani enterocita i ćelijskoj membrani makrofaga za razgradnju, što rezultira smanjenim unosom gvožđa iz hrane i smanjenim oslobađanjem gvožđa iz recikliranih crvenih krvnih zrnaca u MPS (monojedarni sistem fagocita). Gubitak ove funkcije uzrokuje višak gvožđa i hemohromatozu.[10]
Kod infekcija citomegalovirusom, a virusni protein veže se za β2 mikroglobulin, sprečavajući skupljanje molekula MHC klase I i njihov transport do plazmamembrane.
Konstruirani su modeli miševa kojima nedostaje gen β2 mikroglobulina. Ovi miševi pokazuju da je β2 mikroglobulin neophodan za ekspresiju površinsloćelijske MHC klase I i stabilnost brazde koja veže peptide. U stvari, u nedostatku β2 mikroglobulina, na površini se mogu otkriti vrlo ograničene količine molekula MHC klase I (klasični i neklasični) (sindrom golih limfocita ili BLS) . U nedostatku MHC klase I, ne mogu se razviti CD8+ T-ćelija. (CD8+ T-ćelije su podskup T-ćelija uključenih u razvoj stečenog imuniteta.)
Klinički značaj
[uredi | uredi izvor]U pacijenata na dugotrajnoj hemodijalizi, može se agregirati u amiloidna vlakna koja se talože u zglobovima, bolest poznata kao amiloidoza povezana s dijalizom.
Niski nivoi β2 mikroglobulina mogu ukazivati na neprogresivnost HIV-a.[11]
Nivoi β2 mikroglobulin može biti povišen kod multiplog mijeloma i limfoma, iako su u ovim slučajevima primarna amiloidoza (lahki lanac amiloida) i sekundarna amiloidoza (protein povezan sa amiloidima) češći. Normalna vrijednost β2 mikroglobulina je < 2 mg/L.[12] Međutim, s obzirom na multipli mijelom, nivoi β2 mikroglobulina mogu biti i na drugom kraju spektra.[13] Dijagnostičko ispitivanje multiplog mijeloma uključuje dobivanje nivoa β2 mikroglobulina, jer je ovaj nivo važan prognostički pokazatelj. Od 2011., očekuje se da će pacijent sa razinom od < 4 mg/L imati medijanu preživljavanja 43 mjeseca, dok će pacijent sa nivoom > 4 mg/ imati medijanu preživljavanja od samo 12 mjeseci[14] β2 razine mikroglobulina ne mogu, međutim, razlikovati monoklonsku gamopatiju neodređenog značaja (MGUS) koja ima bolju prognozu i tinjajući (nizak stupanj) mijeloma.[15][16]
Zabilježene su mutacije gubitka funkcije ovog gena kod pacijenata sa karcinomom, koji nisu reagirali na imunoterapije
Reference
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- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000060802 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: Beta-2-microglobulin".
- ^ a b Güssow D, Rein R, Ginjaar I, Hochstenbach F, Seemann G, Kottman A, Ploegh HL (novembar 1987). "The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit". Journal of Immunology. 139 (9): 3132–8. PMID 3312414.
- ^ Cunningham BA, Wang JL, Berggård I, Peterson PA (novembar 1973). "The complete amino acid sequence of beta 2-microglobulin". Biochemistry. 12 (24): 4811–22. doi:10.1021/bi00748a001. PMID 4586824.
- ^ Suggs SV, Wallace RB, Hirose T, Kawashima EH, Itakura K (novembar 1981). "Use of synthetic oligonucleotides as hybridization probes: isolation of cloned cDNA sequences for human beta 2-microglobulin". Proceedings of the National Academy of Sciences of the United States of America. 78 (11): 6613–7. Bibcode:1981PNAS...78.6613S. doi:10.1073/pnas.78.11.6613. PMC 349099. PMID 6171820.
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- ^ Hundall SD (2011). "Chapter 3: Iron, Heme, and Hemoglobin". Hematology: A Pathophysiologic Approach (1st izd.). str. 17–25. ISBN 978-0-323-04311-3.
- ^ Rao M, Sayal SK, Uppal SS, Gupta RM, Ohri VC, Banerjee S (oktobar 1997). "Beta-2-Microglobulin Levels in Human-Immunodeficiency Virus Infected Subjects". Medical Journal, Armed Forces India. 53 (4): 251–254. doi:10.1016/S0377-1237(17)30746-3. PMC 5531080. PMID 28769505.
- ^ Pignone M, Nicoll D; McPhee SJ (2004). Pocket guide to diagnostic tests (4th izd.). New York: McGraw-Hill. str. 191. ISBN 0-07-141184-4.
- ^ "Amyloidosis". The Lecturio Medical Concept Library. Pristupljeno 28. 6. 2021.
- ^ Munshi NC, Longo DL, Anderson KC (2011). "Chapter 111: Plasma Cell Disorders". u Loscalzo J, Longo DL, Fauci AS, Dennis LK, Hauser SL (ured.). Harrison's Principles of Internal Medicine (18th izd.). McGraw-Hill Professional. str. 936–44. ISBN 978-0-07-174889-6.
- ^ Rajkumar SV (2005). "MGUS and smoldering multiple myeloma: update on pathogenesis, natural history, and management". Hematology. American Society of Hematology. Education Program. 2005: 340–5. doi:10.1182/asheducation-2005.1.340. PMID 16304401.
- ^ Bataille R, Klein B (novembar 1992). "Serum levels of beta 2 microglobulin and interleukin-6 to differentiate monoclonal gammopathy of undetermined significance". Blood. 80 (9): 2433–4. doi:10.1182/blood.V80.9.2433.2433. PMID 1421418.
Dopunska literatura
[uredi | uredi izvor]- Huang WC, Havel JJ, Zhau HE, Qian WP, Lue HW, Chu CY, et al. (septembar 2008). "Beta2-microglobulin signaling blockade inhibited androgen receptor axis and caused apoptosis in human prostate cancer cells". Clinical Cancer Research. 14 (17): 5341–7. doi:10.1158/1078-0432.CCR-08-0793. PMC 3032570. PMID 18765525.
- Huang WC, Wu D, Xie Z, Zhau HE, Nomura T, Zayzafoon M, et al. (septembar 2006). "beta2-microglobulin is a signaling and growth-promoting factor for human prostate cancer bone metastasis". Cancer Research. 66 (18): 9108–16. doi:10.1158/0008-5472.CAN-06-1996. PMID 16982753.
- Winchester JF, Salsberg JA, Levin NW (oktobar 2003). "Beta-2 microglobulin in ESRD: an in-depth review". Advances in Renal Replacement Therapy. 10 (4): 279–309. doi:10.1053/j.arrt.2003.11.003. PMID 14681859.
- Krangel MS, Orr HT, Strominger JL (decembar 1979). "Assembly and maturation of HLA-A and HLA-B antigens in vivo". Cell. 18 (4): 979–91. doi:10.1016/0092-8674(79)90210-1. PMID 93026.
- Okon M, Bray P, Vucelić D (septembar 1992). "1H NMR assignments and secondary structure of human beta 2-microglobulin in solution". Biochemistry. 31 (37): 8906–15. doi:10.1021/bi00152a030. PMID 1390678.
- Guo HC, Jardetzky TS, Garrett TP, Lane WS, Strominger JL, Wiley DC (novembar 1992). "Different length peptides bind to HLA-Aw68 similarly at their ends but bulge out in the middle". Nature. 360 (6402): 364–6. Bibcode:1992Natur.360..364G. doi:10.1038/360364a0. PMID 1448153. S2CID 4324984.
- Gattoni-Celli S, Kirsch K, Timpane R, Isselbacher KJ (mart 1992). "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 Research. 52 (5): 1201–4. PMID 1737380.
- Saper MA, Bjorkman PJ, Wiley DC (maj 1991). "Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A resolution". Journal of Molecular Biology. 219 (2): 277–319. doi:10.1016/0022-2836(91)90567-P. PMID 2038058.
- Caruana RJ, Lobel SA, Leffell MS, Campbell H, Cheek PL (decembar 1990). "Tumor necrosis factor, interleukin-1 and beta 2-microglobulin levels in chronic hemodialysis patients". The International Journal of Artificial Organs. 13 (12): 794–8. doi:10.1177/039139889001301205. PMID 2289831.
- Connors LH, Shirahama T, Skinner M, Fenves A, Cohen AS (septembar 1985). "In vitro formation of amyloid fibrils from intact beta 2-microglobulin". Biochemical and Biophysical Research Communications. 131 (3): 1063–8. doi:10.1016/0006-291X(85)90198-6. PMID 2413854.
- Hochman JH, Shimizu Y, DeMars R, Edidin M (april 1988). "Specific associations of fluorescent beta-2-microglobulin with cell surfaces. The affinity of different H-2 and HLA antigens for beta-2-microglobulin". Journal of Immunology. 140 (7): 2322–9. PMID 2450918.
- Homma N, Gejyo F, Isemura M, Arakawa M (1989). "Collagen-binding affinity of beta-2-microglobulin, a preprotein of hemodialysis-associated amyloidosis". Nephron. 53 (1): 37–40. doi:10.1159/000185699. PMID 2674742.
- Bataille R, Grenier J, Commes T (1988). "In vitro production of beta 2 microglobulin by human myeloma cells". Cancer Investigation. 6 (3): 271–7. doi:10.3109/07357908809080649. PMID 3048575.
- Hönig R, Marsen T, Schad S, Barth C, Pollok M, Baldamus CA (novembar 1988). "Correlation of beta-2-microglobulin concentration changes to changes of distribution volume". The International Journal of Artificial Organs. 11 (6): 459–64. PMID 3060434.
- Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC (1987). "Structure of the human class I histocompatibility antigen, HLA-A2". Nature. 329 (6139): 506–12. Bibcode:1987Natur.329..506B. doi:10.1038/329506a0. PMID 3309677. S2CID 4373217.
- Güssow D, Rein R, Ginjaar I, Hochstenbach F, Seemann G, Kottman A, Ploegh HL (novembar 1987). "The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit". Journal of Immunology. 139 (9): 3132–8. PMID 3312414.
- Cunningham BA, Wang JL, Berggård I, Peterson PA (novembar 1973). "The complete amino acid sequence of beta 2-microglobulin". Biochemistry. 12 (24): 4811–22. doi:10.1021/bi00748a001. PMID 4586824.
- Suggs SV, Wallace RB, Hirose T, Kawashima EH, Itakura K (novembar 1981). "Use of synthetic oligonucleotides as hybridization probes: isolation of cloned cDNA sequences for human beta 2-microglobulin". Proceedings of the National Academy of Sciences of the United States of America. 78 (11): 6613–7. Bibcode:1981PNAS...78.6613S. doi:10.1073/pnas.78.11.6613. PMC 349099. PMID 6171820.
- Momoi T, Suzuki M, Titani K, Hisanaga S, Ogawa H, Saito A (maj 1995). "Amino acid sequence of a modified beta 2-microglobulin in renal failure patient urine and long-term dialysis patient blood". Clinica Chimica Acta; International Journal of Clinical Chemistry. 236 (2): 135–44. doi:10.1016/0009-8981(95)06039-G. PMID 7554280.
- Collins EJ, Garboczi DN, Karpusas MN, Wiley DC (februar 1995). "The three-dimensional structure of a class I major histocompatibility complex molecule missing the alpha 3 domain of the heavy chain". Proceedings of the National Academy of Sciences of the United States of America. 92 (4): 1218–21. Bibcode:1995PNAS...92.1218C. doi:10.1073/pnas.92.4.1218. PMC 42670. PMID 7862664.
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- Wang Z, Cao Y, Albino AP, Zeff RA, Houghton A, Ferrone S (februar 1993). "Lack of HLA class I antigen expression by melanoma cells SK-MEL-33 caused by a reading frameshift in beta 2-microglobulin messenger RNA". The Journal of Clinical Investigation. 91 (2): 684–92. doi:10.1172/JCI116249. PMC 288010. PMID 8432869.
Vanjski linkovi
[uredi | uredi izvor]- beta 2-Microglobulin na US National Library of Medicine Medical Subject Headings (MeSH)
- Lokacija ljudskog genoma B2M i stranica sa detaljima o genu B2M u UCSC Genome Browseru.
- https://www.ebi.ac.uk/pdbe P61769