タンパク質の翻訳後の改変の体系的な機能的優先順位付け
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
まとめ
科学者は,種間の20万以上の翻訳後の改変 (PTM) サイトを分析しました. 彼らは,機能的に重要なPTMを特定するための方法を開発し,一部のサイトのみが生物学的役割に有意な影響を及ぼすことを明らかにしました.
科学分野:
- 分子生物学は分子生物学である.
- プロテオミクス プロテオミクスは,プロテオミクスの
- バイオインフォマティックス
背景:
- 翻訳後の改変 (PTMs) はタンパク質の機能を調節し,質量スペクトロメトリはPTMの識別を急速に増加させる.
- 特定されたほとんどのPTMの機能的意義は,ほとんど不明のままである.
- PTMを理解することは,複雑な細胞プロセスを解読する上で極めて重要です.
研究 の 目的:
- PTMの機能的関連性を優先する方法を開発する.
- クロスレギュレーション,ドメイン活動,タンパク質とタンパク質の相互作用に関与するPTMを特定する.
- PTMの進化的保存と生物学的重要性を分析する.
主な方法:
- 11種の真核生物から約20万のリン酸化,アセチル化,およびユビキチネーション部位のデータセットをまとめました.
- PTMの機能的関連性を評価するための予測方法を開発しました.
- ドメインファミリー内のPTM保存を分析し,HSP70ドメインファミリーで実験的に検証した結果.
主要な成果:
- ドメインファミリー内の保存されたPTMを,機能的に重要な領域を重複する規制上の"ホットスポット"として特定しました.
- 実験的検証は,HSP70ドメインファミリーにおけるこれらの保存されたPTMの重要性を確認した.
- 分析によると,PTMサイトの一部のみが重要な生物学的役割を持ち,規制相互作用において中立的な漂流の可能性があることを示唆しています.
結論:
- 機能的に関連するPTMの優先順位付けのための枠組みを開発しました.
- PTMの保存は,機能的重要性を示す強力な指標です.
- この研究は,規制上のPTMに対する選択的圧力を強調し,限定されたサブセットが重要な生物学的結果をもたらすことを示唆しています.
関連する概念動画
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...