アンチパラレルエムレ (EmrE) は,非対称な構造の間で交換することで,麻薬を輸出しています
Emma A Morrison1, Gregory T DeKoster, Supratik Dutta
1Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Nature
|December 20, 2011
まとめ
薬剤耐性にとって重要なエシェリキア・コライ EmrE トランスポーターが研究されました. 非対称なアンチパラレル EmrE モノマーが,内向きと外向きの状態を動的に交換し,機能的対称性を説明することを発見しました.
科学分野:
- バイオケミストリー バイオケミストリー
- 構造生物学 構造生物学とは
- メンブレーン輸送 メンブレーン輸送
背景:
- 小型多剤耐性 (SMR) トランスポーターは,活性輸送メカニズムを理解するための鍵です.
- Escherichia coliからのEmrEは,多芳香のカチオン基板を輸出し,多剤耐性を授与します.
- EmrEのホモジマートポロジーは,重要な科学的議論の対象となっている.
研究 の 目的:
- EmrEトランスポーターの構成動態と膜トポロジーを解明する.
- EmrEの構造的非対称性を,その活性部位で観察された機能的対称性と調和させる.
主な方法:
- 溶液核磁気共鳴 (NMR) ダイナミクス実験をバイセルで実施した.
- フォースター共鳴エネルギー転送 (FRET) は,モノメアの方向性を決定します.
- パラマグネティック・リラクゼーション・エンハンスメント (PRE) NMRで,水のアクセシビリティを評価する.
主要な成果:
- 非対称なアンチパラレル EmrE モノマーが内向きと外向きの形状を交換することを実証した.
- 量的に測定された,基板に縛られた EmrE.E. の全局的形状交換ダイナミクスを量化しました.
- EmrE二次体内のモノマーの水へのアクセシビリティの差異を明らかにし,非対称性を示した.
結論:
- EmrEは"動的対称性"を示し,非対称なモノメアは,形状交換を通じて機能的対称性を達成する.
- このダイナミックなメカニズムは,Emergeが構造的非対称性にもかかわらず,どのように輸送活動を維持しているかを説明します.
- 膜タンパク質における活性輸送のための最低限の要件に関する新しい視点を提供します.
関連する概念動画
Chirality in Nature
13.8K
Chirality is the most intriguing yet essential facet of nature, governing life’s biochemical processes and precision. It can be observed from a snail shell pattern in a macroscopic world to an amino acid, the minutest building block of life. Most of the snails around the world have right-coiled shells because of the intrinsic chirality in their genes. All the amino acids present in the human body exist in an enantiomerically pure state, except for glycine - the sole achiral amino acid.
13.8K
ABC Transporters: Exporter
5.7K
ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
5.7K
Export of Misfolded Proteins out of the ER
4.3K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
4.3K
Membrane Asymmetry Regulating Transporters
6.1K
Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
6.1K
Structure-Activity Relationships and Drug Design
1.9K
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...
1.9K
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
735
Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...
735


