低密度脂蛋白受體
外觀
低密度脂蛋白受體(Low-Density Lipoprotein (LDL) Receptor),又稱LDL受體,為一種膜鑲嵌式蛋白質,全長有839個胺基酸(扣掉21胺基酸長的訊息肽)[1]。本受體調控低密度脂蛋白(LDL)的胞吞作用。此種受體專門辨認LDL顆粒上的B100脂蛋白,也可辨認乳糜微粒殘體及中間密度脂蛋白(IDL,極低密度脂蛋白的殘體)上的Apo E。人體LDL受體的基因編碼為LDLR基因[2][3]。屬於低密度脂蛋白受體家族[4]。
Michael S. Brown和Joseph L. Goldstein即因發現LDL受體,以及其與膽固醇代謝的關係[5],而獲得1985年諾貝爾生理醫學獎[6]。
臨床價值
[編輯]功能
[編輯]LDL-膽固醇會和銜接蛋白(adaptin)結合,並在細胞膜中格形蛋白(clathrin)圍住的孔洞中,與LDL受體結合成「LDL受體複合物」。此時,格形蛋白會將LDL-膽固醇吞噬入細胞內,形成囊泡。
突變
[編輯]![](http://upload.wikimedia.org/wikipedia/commons/thumb/d/db/LDLR_pathway.png/220px-LDLR_pathway.png)
- 1類: LDLR沒有完全合成.
- 2類: LDLR沒有正常地從內質網轉運至高爾基體並在細胞表面表達。
- 3類: LDLR沒有正常地在細胞表面與LDL結合,因為載脂蛋白B100(R3500Q)或LDL-R內部有缺陷。
- 4類: LDLR與LDL結合時沒有正常地聚集在網格蛋白包被進行受體介導的內吞作用(途徑中的步驟2)。
- 5類: LDLR沒有被正常地回收至細胞表面(途徑中的步驟5)。
參考文獻
[編輯]- ^ Südhof TC, Goldstein JL, Brown MS, Russell DW. The LDL receptor gene: a mosaic of exons shared with different proteins. Science. May 1985, 228 (4701): 815–22. PMID 2988123. doi:10.1126/science.2988123.
- ^ Francke U, Brown MS, Goldstein JL. Assignment of the human gene for the low density lipoprotein receptor to chromosome 19: synteny of a receptor, a ligand, and a genetic disease. Proc. Natl. Acad. Sci. U.S.A. May 1984, 81 (9): 2826–30. PMC 345163
. PMID 6326146. doi:10.1073/pnas.81.9.2826.
- ^ Lindgren V, Luskey KL, Russell DW, Francke U. Human genes involved in cholesterol metabolism: chromosomal mapping of the loci for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-coenzyme A reductase with cDNA probes. Proc. Natl. Acad. Sci. U.S.A. December 1985, 82 (24): 8567–71. PMC 390958
. PMID 3866240. doi:10.1073/pnas.82.24.8567.
- ^ Nykjaer A, Willnow TE. The low-density lipoprotein receptor gene family: a cellular Swiss army knife?. Trends Cell Biol. June 2002, 12 (6): 273–80 [2015-01-26]. PMID 12074887. doi:10.1016/S0962-8924(02)02282-1. (原始內容存檔於2018-05-01).
- ^ Brown MS, Goldstein JL. How LDL Receptors Influence Cholesterol and Atherosclerosis. Scientific American. 1984, 251 (3): 52–60. PMID 6390676. doi:10.1038/scientificamerican0984-52.
- ^ The Nobel Prize in Physiology or Medicine 1985 (新聞稿). The Royal Swedish Academy of Science. 1985 [2010-07-01]. (原始內容存檔於2011-01-02).
- ^ Low Density Lipoprotein Receptor. LOVD v.1.1.0 - Leiden Open Variation Database. [2015-01-26]. (原始內容存檔於2016-01-28).
延伸閱讀
[編輯]- Brown MS, Goldstein JL. Receptor-mediated endocytosis: insights from the lipoprotein receptor system.. Proc. Natl. Acad. Sci. U.S.A. 1979, 76 (7): 3330–7. PMC 383819
. PMID 226968. doi:10.1073/pnas.76.7.3330.
- Hobbs HH, Brown MS, Goldstein JL. Molecular genetics of the LDL receptor gene in familial hypercholesterolemia.. Hum. Mutat. 1993, 1 (6): 445–66. PMID 1301956. doi:10.1002/humu.1380010602.
- Fogelman AM, Van Lenten BJ, Warden C; et al. Macrophage lipoprotein receptors.. J. Cell Sci. Suppl. 1989, 9: 135–49. PMID 2855802.
- Barrett PH, Watts GF. Shifting the LDL-receptor paradigm in familial hypercholesterolemia: novel insights from recent kinetic studies of apolipoprotein B-100 metabolism.. Atherosclerosis. Supplements. 2002, 2 (3): 1–4. PMID 11923121. doi:10.1016/S1567-5688(01)00012-5.
- May P, Bock HH, Herz J. Integration of endocytosis and signal transduction by lipoprotein receptors.. Sci. STKE. 2003, 2003 (176): PE12. PMID 12671190. doi:10.1126/stke.2003.176.pe12.
- Gent J, Braakman I. Low-density lipoprotein receptor structure and folding.. Cell. Mol. Life Sci. 2004, 61 (19-20): 2461–70. PMID 15526154. doi:10.1007/s00018-004-4090-3.
外部連結
[編輯]- Description of LDL receptor pathway at the Brown - Goldstein Laboratory webpage(頁面存檔備份,存於互聯網檔案館)
- 醫學主題詞表(MeSH):LDL+Receptor
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