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ABC Transporters: Exporter01:31

ABC Transporters: Exporter

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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...
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Nuclear Export of mRNA

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Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
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The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
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A eukaryotic cell can have up to three different types of genetic systems: nuclear, mitochondrial, and chloroplast. During evolution, organelles have exported many genes to the nucleus; this transfer is still ongoing in some plant species. Approximately 18% of the Arabidopsis thaliana nuclear genome is thought to be derived from the chloroplast’s cyanobacterial ancestor, and around 75% of the yeast genome derived from the mitochondria’s bacterial ancestor. This export has occurred...
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ABC エクスポーター MsbA の未知の核酸結合モード

Hundeep Kaur1, Bárbara Abreu2, Dmitry Akhmetzyanov3

  • 1Institute for Biophysical Chemistry & Centre for Biomolecular Magnetic Resonance , Goethe-University Frankfurt , 60438 Frankfurt , Germany.

Journal of the American Chemical Society
|October 6, 2018
PubMed
まとめ

ABCトランスポーターMsbAは,QループとHisスイッチの近くの追加部位で核酸を結合し,結合ATPアゼと逆アデニラートキナーゼ活動に不可欠である. この発見により,ABCタンパク質における核酸結合の構造的メカニズムが明らかになった.

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科学分野:

  • 生物化学
  • 構造生物学
  • 膜タンパク質

背景:

  • ATP結合カセット (ABC) トランスポーター MsbAは,ATP駆動のリピドAフリッパースとして機能する.
  • MsbAは,ATPの水解のために核酸結合ドメイン (NBD) を利用するABCタンパク質スーパーファミリーに属します.
  • MsbAは最近,ATPの水解と逆アデニル酸キナーゼ (rAK) のような反応の両方を実行し,二重の触媒作用を示した.

研究 の 目的:

  • MsbAにおけるヌクレオチド結合の構造的基礎を調査する.
  • 結合されたATPase-rAK活動のメカニズムを解明する.
  • MsbAの触媒サイクル内のヌクレオチドの相互作用を特徴づけるために.

主な方法:

  • 固体NMR (従来型とDNP強化型)
  • パルス電子パラマグネティック共振 (EPR) スペクトロスコーピー
  • 分子力学 (MD) のシミュレーション

主要な成果:

  • QループとHISスイッチの近くで 核酸結合部位を特定した
  • この部位が基本的な金属イオン調整 (Mn2+をMg2+の代替物として使用) に干渉しないことが実証された.
  • MDシミュレーションは,ニュクレオチドの位置,方向,結合モードを詳細に記述し,実験的発見を裏付けました.

結論:

  • 新しく特定された核酸結合部位は,MsbAの結合ATPase-rAKメカニズムに不可欠です.
  • MsbAのヌクレオチド結合に関する構造的な洞察は,ABCトランスポーター機能の理解を進める.
  • この研究は,MsbA触媒におけるニュクレオチドと金属イオンの相互作用の詳細なメカニズムを示している.