金属ケラート型ABCトランスポーターの内部向きの形状
1Division of Chemistry and Chemical Engineering, Howard Hughes Medical Institute, MC 114-96, California Institute of Technology (Caltech), Pasadena, CA 91125, USA.
まとめ
Haemophilus influenzaeのATP結合カセット (ABC) トランスポーターの結晶構造が解明され,内向きの浸透経路が明らかになった. この発見は,ABCトランスポーターにおける基板転位の交替アクセスメカニズムについての洞察を提供します.
科学分野:
- 構造生物学 構造生物学とは
- 分子微生物学 分子微生物学
- バイオケミストリー バイオケミストリー
背景:
- アデノシン三リン酸 (ATP) 結合カセット (ABC) トランスポーターは,基板転位に関与する重要な膜タンパク質です.
- ABCトランスポーターの構造動態を理解することは,それらの輸送機構を明らかにする鍵です.
研究 の 目的:
- Haemophilus influenzae.からのHI1470/HI1471 ABCトランスポーターの結晶構造を決定する.
- 構造をBtuCDのような同型トランスポーターと比較して,形状の変化を理解する.
主な方法:
- X線結晶グラフィーです.
- 高解像度構造決定 (2.4アングストーム)
- 比較的な構造分析
主要な成果:
- HI1470/HI1471 ABCトランスポーターの結晶構造が解明され,内向きの浸透経路が明らかになりました.
- 外向きのBtuCDトランスポーターと比較して,膜を横断するサブユニットの翻訳的シフトと位置変更を含む重要な構造的な違いが観察されました.
- これらの差異は,交代アクセスメカニズムに関連する異なる形状状態を示唆しています.
結論:
- 決定された構造は,このABCトランスポーターの内向きの形状のモデルを提供します.
- 観測された構造的変動は,ABC輸送業者の柔軟性と,輸送のために異なる状態を採用する能力を強調しています.
- この研究は,ABCトランスポーターにおける基板転位機構の理解に貢献します.
関連する概念動画
ABC Transporters: Exporter
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...
ABC Transporters: Importer
ATP-binding cassette or ABC transporters are a class of ATP-driven pumps that hydrolyze ATP to move solutes across the membrane. They can be grouped into importers and exporters. While exporters are present in all domains of life, importers exist only in bacteria and some plants.
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
The ADP/ATP Carrier Protein
ADP/ATP carrier or AAC protein is the most abundant carrier protein in the inner mitochondrial membrane. It transports large quantities of ADP and ATP, equivalent to the average human body weight, every day. Among other transporters, ACC protein is one of the best-studied members of the mitochondrial carrier protein family. The ADP/ATP carrier protein comprises two transmembrane helices connected to a loop and a single alpha-helix on the matrix side. It switches between two conformational...
Carrier-Mediated Transport
Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Protein Transport into the Inner Mitochondrial Membrane
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Translocation of Proteins into the Mitochondria
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...


