翻訳後のポリグリサイレーションのための酵素機構の進化的分岐
Krzysztof Rogowski1, François Juge, Juliette van Dijk
1CRBM, CNRS, Université Montpellier 2 and 1, Montpellier, France.
Cell
|June 16, 2009
まとめ
研究者らは,タンパク質を改変するグリシンリガスを発見し,多糖化がドロソフィラの発達と生育に不可欠であることを明らかにした. いくつかのヒト酵素は活性を失っている可能性があり,特定の機能には単糖化が十分であることを示唆しています.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- ポリグリサイレーションは,タンパク質にグリシン側鎖を加えるような翻訳後の改変である.
- この変異は,微小管の重要な成分であるチューブリンに特に顕著です.
- ポリグリサイル化に起因する酵素とその機能的意義は,まだ完全に理解されていません.
研究 の 目的:
- タンパク質のポリグリサイレーションに責任を負う酵素を特定し,特徴づけること.
- ポリグリサイレーションの機能的役割を in vivo,特にモデル生物で調査する.
- 哺乳類とドロソフィラとの間のグリサイラゼ機能の進化的違いを探求する.
主な方法:
- 保存されたグリシンリガゼのファミリーの特定.
- 哺乳類およびドロソフィラのグリサイラゼの触媒機構を決定するための酵素分析.
- ドロソフィラのRNA干渉 (RNAi) は,グリセラーゼの活性を低下させる.
- グリチラゼ欠乏型ドロソフィラのフェノタイプ分析,生育能力と発達評価を含む.
主要な成果:
- 保存されたグリシンリガゼの一族が特定され,異なる酵素機構を通じてタンパク質ポリグリサイレーションを触媒化した.
- 哺乳類のグリサイラゼは,2つの異なる酵素タイプ (初期化および延長) として機能するが,ドロソフィラのグリサイラゼは二機能である.
- ヒトの延長型グリサイラゼは酵素活性を失っており,モノグリサイレーションがいくつかの機能に十分である可能性があることを示唆しています.
- ドロソフィラのグリサイラゼの減少は,総グリサイレーション,男性不妊,および発達死亡率の減少につながり,タンパク質グリサイレーションの重要な役割を強調しました.
結論:
- タンパク質のポリグリサイレーションは,多様な酵素機構を持つ保存されたグリシンリガゼの家族によって媒介されます.
- ポリグリサイレーションは,精子の個体化,軸索膜の維持,胚の発達など,複数の生物学的プロセスに不可欠です.
- グリサイラゼの機能における進化的差異は,ヒトのようないくつかの種において,モノグリサイレーションへの潜在的なシフトを示唆する.
- これらの発見は,細胞機能におけるタンパク質グリキュレーションの一般的で重要な役割を示しています.
関連する概念動画
01:24Oligosaccharide Assembly
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
01:29Protein Folding Quality Check in the RER
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
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.
01:25Protein Glycosylation
Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
Glycosylation occurs in...
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.
01:57Protein Complexes with Interchangeable Parts
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...