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翻译后修饰

胰岛素的翻译后修饰。 At the top, the ribosome translates a mRNA sequence into a protein, insulin, and passes the protein through the endoplasmic reticulum, where it is cut, folded, and held in shape by disulfide (-S-S-) bonds. Then the protein passes through the golgi apparatus, where it is packaged into a vesicle. In the vesicle, more parts are cut off, and it turns into mature insulin.

翻译后修饰(英语:Post-translational modification,缩写PTM;又称后翻译修饰)是指蛋白质翻译后的化学修饰。对于大部分的蛋白质来说,这是蛋白质生物合成的较后步骤。PTM是细胞信号传导中的重要组成部分。

蛋白质,或是多肽,是多条或一条氨基酸的链。当合成蛋白质时,20种不同的氨基酸会合并成为蛋白质。氨基酸的转译后修饰会附在蛋白质其他的生物化学官能团(如醋酸盐磷酸盐、不同的脂类碳水化合物)、改变氨基酸的化学性质,或是造成结构的改变(如建立双硫键),来扩阔蛋白质的功能。

再者,可以从蛋白质的N末端移除氨基酸,或从中间将链剪开。举例来说,胰岛素是肽的激素,它会在建立双硫键后被剪开两次,并在链的中间移走多肽前体,而形成的蛋白质包含了两条以双硫键连接的多肽链。

其他修饰,就像磷酸化,是控制蛋白质活动机制的一部分。蛋白质活动可以是令酶活性化或钝化。

加入官能团

翻译后修饰包括以下加入官能团的反应:

加入其他蛋白质或肽

  • 干扰素激活基因化——与干扰素激活基因15(ISG15)蛋白质建立共价键[1]
  • 小泛素相关修饰化——与小泛素相关修饰子蛋白建立共价键。[2]
  • 泛素化——与泛素建立共价键。

改变氨基酸的化学性质

结构改变

数据库与工具

Flowchart of the process and the data sources to predict PTMs.[3]

蛋白质序列包含通过修饰酶识别的序列基序,并且可以在 PTM 数据库中记录或预测。 随着发现大量不同的修改,需要在数据库中记录此类信息。 PTM 信息可以通过实验手段收集,也可以从高质量、手动整理的数据中预测。 已经创建了许多数据库,通常侧重于某些分类群(例如人类蛋白质)或其他特征。

资源列表

  • PhosphoSitePlus页面存档备份,存于互联网档案馆[4] – 用于研究哺乳动物蛋白质翻译后修饰的综合信息和工具数据库
  • ProteomeScout[5] – 实验性蛋白质和翻译后修饰数据库
  • Human Protein Reference Database[5] – 用于不同修饰和了解不同蛋白质、它们的类别以及与致病蛋白质相关的功能/过程的数据库
  • PROSITE[6] – 包括网站在内的多种类型 PTM 的共识模式数据库

工具

蛋白质及其 PTM 可视化软件列表

  • PyMOL[7]——将一组常见的 PTM 引入蛋白质模型
  • AWESOME[8] – 查看单核苷酸多态性对 PTM 的作用的交互式工具
  • Chimera[9] – 可视化分子的交互式数据库

案例

参考文献

  1. ^ Malakhova, Oxana A.; Yan, Ming; Malakhov, Michael P.; Yuan, Youzhong; Ritchie, Kenneth J.; Kim, Keun Il; Peterson, Luke F.; Shuai, Ke; and Dong-Er Zhang. Protein ISGylation modulates the JAK-STAT signaling pathway. Genes & Development. 2003, 17 (4): 455–460 [2006-11-22]. (原始内容存档于2008-07-19). 
  2. ^ Van G. Wilson , 编. Sumoylation: Molecular Biology and Biochemistry. Horizon Bioscience. 2004. ISBN 978-0-9545232-8-2. (原始内容存档于2005-02-09). 
  3. ^ Lee TY, Huang HD, Hung JH, Huang HY, Yang YS, Wang TH. dbPTM: an information repository of protein post-translational modification. Nucleic Acids Research. January 2006, 34 (Database issue): D622–7. PMC 1347446可免费查阅. PMID 16381945. doi:10.1093/nar/gkj083. 
  4. ^ Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E. PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Research. January 2015, 43 (Database issue): D512–20. PMC 4383998可免费查阅. PMID 25514926. doi:10.1093/nar/gku1267. 
  5. ^ 5.0 5.1 Goel R, Harsha HC, Pandey A, Prasad TS. Human Protein Reference Database and Human Proteinpedia as resources for phosphoproteome analysis. Molecular BioSystems. February 2012, 8 (2): 453–63. PMC 3804167可免费查阅. PMID 22159132. doi:10.1039/c1mb05340j. 
  6. ^ Sigrist CJ, Cerutti L, de Castro E, Langendijk-Genevaux PS, Bulliard V, Bairoch A, Hulo N. PROSITE, a protein domain database for functional characterization and annotation. Nucleic Acids Research. January 2010, 38 (Database issue): D161–6. PMC 2808866可免费查阅. PMID 19858104. doi:10.1093/nar/gkp885. 
  7. ^ Warnecke A, Sandalova T, Achour A, Harris RA. PyTMs: a useful PyMOL plugin for modeling common post-translational modifications. BMC Bioinformatics. November 2014, 15 (1): 370. PMC 4256751可免费查阅. PMID 25431162. doi:10.1186/s12859-014-0370-6. 
  8. ^ Yang Y, Peng X, Ying P, Tian J, Li J, Ke J, Zhu Y, Gong Y, Zou D, Yang N, Wang X, Mei S, Zhong R, Gong J, Chang J, Miao X. AWESOME: a database of SNPs that affect protein post-translational modifications. Nucleic Acids Research. January 2019, 47 (D1): D874–D880. PMC 6324025可免费查阅. PMID 30215764. doi:10.1093/nar/gky821. 
  9. ^ Morris JH, Huang CC, Babbitt PC, Ferrin TE. structureViz: linking Cytoscape and UCSF Chimera. Bioinformatics. September 2007, 23 (17): 2345–7. PMID 17623706. doi:10.1093/bioinformatics/btm329可免费查阅. 
  10. ^ 1tp8 - Proteopedia, life in 3D. www.proteopedia.org. [2023-04-18]. (原始内容存档于2009-08-28). 

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翻译后修饰
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