活性化前に完全に組み立てられたSaccharomyces cerevisiae spliceosomeの構造
Rui Bai1, Ruixue Wan1, Chuangye Yan1
1Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, Schools of Life Sciences and Medicine, Tsinghua University, Beijing 100084, China.
Science (New York, N.Y.)
|May 26, 2018
まとめ
研究者は酵母スプリセオソームを視覚化しました
科学分野:
- 分子生物学
- 構造生物学
- 生物化学
背景:
- スプライソームは 遺伝子発現に不可欠な ダイナミックな分子機構です
- スプライソームの組立と活性化を理解することは,遺伝子調節を解読するために極めて重要です.
- プレ-BとB複合体は,スプライソーム触媒の重要な中間段階を表しています.
研究 の 目的:
- Saccharomyces cerevisiae pre-BとB spliceosome複合体の高解像度構造を決定する.
- スプライソームの組み立てと活性化に伴う分子メカニズムを解明する.
- これらの初期の触媒的ステップにおける特定のタンパク質とRNAの相互作用の役割を特定する.
主な方法:
- 構造を解明するために冷凍電子顕微鏡 (cryo-EM) が使われました.
- 高解像度構造分析は,精製された酵母スプライソーム複合体で行われました.
- 構造的な発見を検証するために生化学的および生体物理的な技術が使用されました.
主要な成果:
- 前BおよびB複合体の冷凍-EM構造は3. 3~4. 6 Åの解像度で決定された.
- Yhc1,Luc7による5' スプライスサイト認識,およびプレ-B複合体のSmリングを含む主要なRNA-タンパク質相互作用が視覚化されました.
- U1小核リボヌクレオプロテイン (snRNP) の解離とB複合体内のU6 snRNA近くの5'- エクソン - 5' SS配列の転位が観察されました.
- U6 snRNAがU5 snRNAループIに固定され,SF3b複合体による分岐点配列-U2 snRNA複合体の認識は,両方の構造で確認された.
結論:
- この研究は,前例のない構造的な洞察をB前とB前段階の酵母スプライソームに提供しています.
- これらの構造は,スピライソームの組立と活性化を制御するダイナミックな再配置とタンパク質-RNAの相互作用を明らかにします.
- この発見は,スプライセソームがどのように構築され,触媒として活性化されるのかについてのメカニズム的な理解を提供します.
関連する概念動画
01:32Assembly of Complex Microtubule Structures
2.5K
Complex microtubule structures are present in resting cells and in dividing cells. In resting cells, they are responsible for maintaining the cellular architecture, tracks for intracellular transport, positioning of organelles, assembly of cilia and flagella. They mediate the bipolar spindle assembly for chromosomal segregation and positioning of the cell division plate in dividing cells. The formation of microtubule complex structures depends on the cell type, cell stage, and cell function.
2.5K
02:41Chromatin Structure Regulates pre-mRNA Processing
8.2K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
8.2K
01:28Structure-Activity Relationships and Drug Design
1.8K
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
1.8K
02:41Protein Complex Assembly
16.8K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
16.8K
01:29Cholinergic Antagonists: Chemistry and Structure-Activity Relationship
2.8K
Cholinergic antagonists bind to cholinergic receptors and limit the effects of acetylcholine and other cholinergic agonists. Based on the specific cholinergic receptor affinity, these antagonists are classified as muscarinic or nicotinic. Anticholinergics interrupt parasympathetic innervations while sympathetic innervations remain uninterrupted. Muscarinic antagonists are also called 'muscarinic antagonists', 'antimuscarinics', or 'parasympatholytics'. Nicotinic...
2.8K
01:16Adrenergic Agonists: Chemistry and Structure-Activity Relationship
3.9K
Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
3.9K