β2-微球蛋白
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β2微球蛋白(英語:β2-microglobulin,縮寫B2M)是MHC1類分子分子的組成部分之一,在所有有核的細胞中(即不包括紅血球)都有表達[6][7]。在人類基因組中,β2微球蛋白[8]由B2M 基因所編碼[7][9]。
結構功能
[編輯]![](http://upload.wikimedia.org/wikipedia/commons/thumb/d/d2/MHC_Class_1%28Traditional_Chinese%29.svg/220px-MHC_Class_1%28Traditional_Chinese%29.svg.png)
β2-微球蛋白位於細胞表面的α3鏈旁,但與α鏈不同的是,β2並沒有跨膜區域,且為非共價結合。在β2的「上方」(指遠離細胞膜的一端)為α鏈的α1區和α2區,構成了MHC的肽結合區。
β2微球蛋白不止參與形成第一類MHC分子,還能組成與之類似的表面受體,如CD1和Qa等。
β2微球蛋白還有一個功能,就是能與HFE蛋白結合,來調控鐵調素在肝臟中的表達。鐵調素會與腸上皮細胞和巨噬細胞膜上的膜鐵轉運蛋白作用。可以降低食物中和紅血球回收的鐵質攝取,該功能的喪失會導致鐵過量和血色沉着病。
臨床意義
[編輯]在長期血液透析的患者中,β2微球蛋白可以聚集成澱粉樣纖維沉積在關節間隙,這種疾病被稱為透析相關澱粉樣變性。
缺乏β2微球蛋白基因的小鼠模型已經被改造。這些小鼠證明β2微球蛋白對於MHC Ⅰ類分子的細胞表面表達和肽結合溝的穩定性是必需的。事實上,在沒有β2微球蛋白的情況下,可以在表面檢測到數量非常有限的MHC I類分子。在沒有MHC I類分子的情況下,CD8 T細胞不能生長(CD8 T細胞是參與獲得性免疫發展的T細胞的一個子集)。低水平的β2微球蛋白可顯示HIV的非進展性。
多發性骨髓瘤和淋巴瘤的β-2微球蛋白水平可能升高,但在這些情況下,原發性澱粉樣變性(澱粉樣輕鏈)和繼發性澱粉樣變性(澱粉樣相關蛋白)更常見。β-2微球蛋白的正常值為<2 mg/L[10]。 然而,對於多發性骨髓瘤,β2微球蛋白的水平也可能處於譜的另一端。多發性骨髓瘤的診斷檢測包括獲取β2微球蛋白水平,因為該水平是一個重要的預後指標,水平<4 mg/L的患者的中位生存期預計為43個月,而水平>4 mg/L的患者的中位生存期僅為12個月[11]。β-2微球蛋白水平不能區分預後較好的不確定意義的單克隆免疫球蛋白血症(MGUS)和隱匿性(低度)骨髓瘤[12][13]。
參考文獻
[編輯]- ^ 與Β2微球蛋白相關的疾病;在維基數據上查看/編輯參考.
- ^ 2.0 2.1 2.2 GRCh38: Ensembl release 89: ENSG00000166710、ENSG00000273686 - Ensembl, May 2017
- ^ 3.0 3.1 3.2 GRCm38: Ensembl release 89: ENSMUSG00000060802 - Ensembl, May 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.
- ^ B2M beta-2-microglobulin [Homo sapiens (human)]. NCBI. [2022-03-16] (英語).
- ^ 7.0 7.1 Güssow, D.; Rein, R.; Ginjaar, I.; Hochstenbach, F.; Seemann, G.; Kottman, A.; Ploegh, H. L. The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit. Journal of Immunology (Baltimore, Md.: 1950). 1987-11-01, 139 (9): 3132–3138 [2022-03-16]. ISSN 0022-1767. PMID 3312414. (原始內容存檔於2022-01-05).
- ^ Cunningham, Bruce A.; Wang, John L.; Berggard, Ingemar; Peterson, Per A. Complete amino acid sequence of β 2 -microglobulin. Biochemistry. 1973-11, 12 (24): 4811–4822 [2022-03-16]. ISSN 0006-2960. PMID 4586824. doi:10.1021/bi00748a001. (原始內容存檔於2022-03-16) (英語).
- ^ Suggs, S V; Wallace, R B; Hirose, T; Kawashima, E H; Itakura, K. Use of synthetic oligonucleotides as hybridization probes: isolation of cloned cDNA sequences for human beta 2-microglobulin.. Proceedings of the National Academy of Sciences. 1981-11, 78 (11): 6613–6617. ISSN 0027-8424. PMC 349099
. PMID 6171820. doi:10.1073/pnas.78.11.6613 (英語).
- ^ Pignone M, Nicoll D; McPhee SJ. Pocket guide to diagnostic tests 4th. New York: McGraw-Hill. 2004: 191. ISBN 0-07-141184-4.
- ^ Munshi NC, Longo DL, Anderson KC. Chapter 111: Plasma Cell Disorders. Loscalzo J, Longo DL, Fauci AS, Dennis LK, Hauser SL (編). Harrison's Principles of Internal Medicine 18th. McGraw-Hill Professional. 2011: 936–44. ISBN 0-07-174889-X.
- ^ Rajkumar, S. Vincent. MGUS and Smoldering Multiple Myeloma: Update on Pathogenesis, Natural History, and Management. Hematology. 2005-01-01, 2005 (1): 340–345 [2022-03-16]. ISSN 1520-4391. doi:10.1182/asheducation-2005.1.340. (原始內容存檔於2022-03-16) (英語).
- ^ Bataille, R; Klein, B. Serum levels of beta 2 microglobulin and interleukin-6 to differentiate monoclonal gammopathy of undetermined significance [letter; comment]. Blood. 1992-11-01, 80 (9): 2433–2434. ISSN 0006-4971. doi:10.1182/blood.V80.9.2433.bloodjournal8092433 (英語).
延伸閱讀
[編輯]- Huang, Wen-Chin; Havel, Jonathan J.; Zhau, Haiyen E.; Qian, Wei Ping; Lue, Hui-Wen; Chu, Chia-Yi; Nomura, Takeo; Chung, Leland W.K. β2-Microglobulin Signaling Blockade Inhibited Androgen Receptor Axis and Caused Apoptosis in Human Prostate Cancer Cells. Clinical Cancer Research. 2008-09-01, 14 (17): 5341–5347. ISSN 1078-0432. PMC 3032570
. PMID 18765525. doi:10.1158/1078-0432.CCR-08-0793 (英語).
- Huang, Wen-Chin; Wu, Daqing; Xie, Zhihui; Zhau, Haiyen E.; Nomura, Takeo; Zayzafoon, Majd; Pohl, Jan; Hsieh, Chia-Ling; Weitzmann, M. Neale. β2-Microglobulin Is a Signaling and Growth-Promoting Factor for Human Prostate Cancer Bone Metastasis. Cancer Research. 2006-09-15, 66 (18): 9108–9116. ISSN 0008-5472. PMID 16982753. doi:10.1158/0008-5472.CAN-06-1996 (英語).
- Winchester, James F; Salsberg, Jamie A; Levin, Nathan W. Beta-2 microglobulin in ESRD: an in-depth review. Advances in Renal Replacement Therapy. 2003-10, 10 (4): 279–309 [2022-03-16]. PMID 14681859. doi:10.1053/j.arrt.2003.11.003. (原始內容存檔於2022-03-03) (英語).
- Okon, Mark; Bray, Paul; Vucelic, Dusan. Proton NMR assignments and secondary structure of human .beta.2-microglobulin in solution. Biochemistry. 1992-09-22, 31 (37): 8906–8915 [2022-03-16]. ISSN 0006-2960. doi:10.1021/bi00152a030. (原始內容存檔於2022-03-16) (英語).
- Guo, Hwai-Chen; Jardetzky, Theodore S.; Garrettt, Thomas P. J.; Lane, William S.; Strominger, Jack L.; Wiley, Don C. Different length peptides bind to HLA-Aw68 similarly at their ends but bulge out in the middle. Nature. 1992-11, 360 (6402): 364–366 [2022-03-16]. ISSN 0028-0836. PMID 1448153. doi:10.1038/360364a0. (原始內容存檔於2022-03-14) (英語).
- Gattoni-Celli, S.; Kirsch, K.; Timpane, R.; Isselbacher, K. J. 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. 1992-03-01, 52 (5): 1201–1204 [2022-03-16]. ISSN 0008-5472. PMID 1737380. (原始內容存檔於2022-03-16).
- Saper, M.A.; Bjorkman, P.J.; Wiley, D.C. Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 Å resolution. Journal of Molecular Biology. 1991-05, 219 (2): 277–319 [2022-03-16]. PMID 2038058. doi:10.1016/0022-2836(91)90567-P. (原始內容存檔於2022-03-03) (英語).
- Caruana, R. J.; Lobel, S. A.; Leffell, M. S.; Campbell, H.; Cheek, P. L. Tumor necrosis factor, interleukin-1 and beta 2-microglobulin levels in chronic hemodialysis patients. The International Journal of Artificial Organs. 1990-12, 13 (12): 794–798 [2022-03-16]. ISSN 0391-3988. PMID 2289831. (原始內容存檔於2022-03-16).
- Connors, L.H.; Shirahama, T.; Skinner, M.; Fenves, A.; Cohen, A.S. In vitro formation of amyloid fibrils from intact β2-microglobulin. Biochemical and Biophysical Research Communications. 1985-09, 131 (3): 1063–1068 [2022-03-16]. PMID 2413854. doi:10.1016/0006-291X(85)90198-6. (原始內容存檔於2019-12-05) (英語).
- Hochman, J. H.; Shimizu, Y.; DeMars, R.; Edidin, M. 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 (Baltimore, Md.: 1950). 1988-04-01, 140 (7): 2322–2329 [2022-03-16]. ISSN 0022-1767. PMID 2450918. (原始內容存檔於2022-03-16).
- Homma, Noriyuki; Gejyo, Fumitake; Isemura, Mamoru; Arakawa, Masaaki. Collagen-Binding Affinity of Beta-2-Microglobulin, a Preprotein of Hemodialysis-Associated Amyloidosis. Nephron. 1989, 53 (1): 37–40. ISSN 1660-8151. PMID 2674742. doi:10.1159/000185699 (英語).
- Bataille, Régis; Grenier, Jean; Commes, Thérèse. In Vitro Production of Beta 2 Microglobulin by Human Myeloma Cells. Cancer Investigation. 1988-01, 6 (3): 271–277. ISSN 0735-7907. PMID 3048575. doi:10.3109/07357908809080649 (英語).
- Hönig, R.; Marsen, T.; Schad, S.; Barth, C.; Pollok, M.; Baldamus, C. A. Correlation of beta-2-microglobulin concentration changes to changes of distribution volume. The International Journal of Artificial Organs. 1988-11, 11 (6): 459–464 [2022-03-16]. ISSN 0391-3988. PMID 3060434. (原始內容存檔於2022-03-16).
- Bjorkman, P. J.; Saper, M. A.; Samraoui, B.; Bennett, W. S.; Strominger, J. L.; Wiley, D. C. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987-10, 329 (6139): 506–512 [2022-03-16]. ISSN 0028-0836. PMID 3309677. doi:10.1038/329506a0. (原始內容存檔於2022-03-16) (英語).
- Güssow, D.; Rein, R.; Ginjaar, I.; Hochstenbach, F.; Seemann, G.; Kottman, A.; Ploegh, H. L. The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit. Journal of Immunology (Baltimore, Md.: 1950). 1987-11-01, 139 (9): 3132–3138 [2022-03-16]. ISSN 0022-1767. PMID 3312414. (原始內容存檔於2022-01-05).
- Cunningham, Bruce A.; Wang, John L.; Berggard, Ingemar; Peterson, Per A. Complete amino acid sequence of β 2 -microglobulin. Biochemistry. 1973-11, 12 (24): 4811–4822 [2022-03-16]. ISSN 0006-2960. PMID 4586824. doi:10.1021/bi00748a001. (原始內容存檔於2022-03-16) (英語).
- Suggs, S V; Wallace, R B; Hirose, T; Kawashima, E H; Itakura, K. Use of synthetic oligonucleotides as hybridization probes: isolation of cloned cDNA sequences for human beta 2-microglobulin.. Proceedings of the National Academy of Sciences. 1981-11, 78 (11): 6613–6617. ISSN 0027-8424. PMC 349099
. PMID 6171820. doi:10.1073/pnas.78.11.6613 (英語).
- Momoi, Tomoko; Suzuki, Masami; Titani, Koiti; Hisanaga, Shuichi; Ogawa, Hiroshi; Saito, Akira. Amino acid sequence of a modified β2-microglobulin in renal failure patient urine and long-term dialysis patient blood. Clinica Chimica Acta. 1995-05, 236 (2): 135–144 [2022-03-16]. PMID 7554280. doi:10.1016/0009-8981(95)06039-G. (原始內容存檔於2019-12-03) (英語).
- Collins, E J; Garboczi, D N; Karpusas, M N; Wiley, D C. 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. 1995-02-14, 92 (4): 1218–1221. ISSN 0027-8424. PMC 42670
. PMID 7862664. doi:10.1073/pnas.92.4.1218 (英語).
- Ryo, Matoba; Kousaku, Okubo; Naohiro, Hori; Atsushi, Fukushima; Kenichi, Matsubara. The addition of 5′-coding information to a 3′-directed cDNA library improves analysis of gene expression. Gene. 1994-09, 146 (2): 199–207 [2022-03-16]. PMID 8076819. doi:10.1016/0378-1119(94)90293-3. (原始內容存檔於2019-12-04) (英語).
- Wang, Z; Cao, Y; Albino, A P; Zeff, R A; Houghton, A; Ferrone, S. Lack of HLA class I antigen expression by melanoma cells SK-MEL-33 caused by a reading frameshift in beta 2-microglobulin messenger RNA.. Journal of Clinical Investigation. 1993-02-01, 91 (2): 684–692 [2022-03-16]. ISSN 0021-9738. PMC 288010
. PMID 8432869. doi:10.1172/JCI116249. (原始內容存檔於2019-12-29) (英語).
外部連結
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