蛋白质翻译后修改的系统功能优先级
Pedro Beltrao1, Véronique Albanèse, Lillian R Kenner
1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94107, USA. pedro.beltrao@ucsf.edu
Cell
|July 24, 2012
概括
科学家分析了超过20万个跨物种的翻译后修改 (PTM) 站点. 他们开发了识别功能性重要PTM的方法,揭示了只有很少一部分地点对生物作用有重大影响.
科学领域:
- 分子生物学分子生物学
- 蛋白质组学是指蛋白质组学.
- 生物信息学是一种生物信息学.
背景情况:
- 翻译后修饰 (PTMs) 调节蛋白质功能,质谱学迅速增加了PTM的识别.
- 大多数已识别的PTM的功能意义仍然在很大程度上是未知的.
- 了解PTM对于破译复杂的细胞过程至关重要.
研究的目的:
- 开发方法来优先考虑PTM的功能相关性.
- 确定涉及交叉调节,域活性和蛋白质与蛋白质相互作用的PTM.
- 分析PTMs的进化保护和生物学意义.
主要方法:
- 编制了来自11个真核生物物种的约20万个酸化,乙化和无处不在的数据集.
- 开发预测方法来评估PTM的功能相关性.
- 分析了域名家族内的PTM保护,并对HSP70域名家族的实验验证结果.
主要成果:
- 在域名家族内确定了保留的PTM,作为重叠功能重要区域的监管"热点".
- 实验验证证了这些保存的PTM在HSP70域家族中的重要性.
- 分析表明,只有很少一部分PTM遗址具有重要的生物作用,在监管相互作用中可能存在中立漂移.
结论:
- 制定了一个框架,以优先考虑功能相关的PTM.
- 维护PTM是一个功能重要性的强有力的指标.
- 该研究强调了对监管PTM的选择性压力,并表明有限的子集推动了重要的生物结果.
相关概念视频
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
01:02Phosphorylation
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
02:54Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
01:26Protein Modifications in the RER
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
01:26Bacterial Protein Maturation
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
01:23Regulation of Expression at Multiple Steps
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...