W546堆叠中断将人类氨酸输送器ABCB6陷入一个面向外的短暂状态
Sang Soo Lee1, Jun Gyou Park1, Eunhong Jang1
1School of Life Sciences, GIST, 123 Cheomdan-gwagiro, Buk-gu, Gwangju, 61005, Republic of Korea.
Communications biology
|September 22, 2023
概括
人类ATP结合盒载体亚家族B6 (ABCB6) 中的W546A突变破坏了其正常功能. 然而,纳米磁盘中的脂相互作用恢复了ABCB6转运器的功能.
科学领域:
- 生物化学 生化学
- 结构生物学 结构生物学
- 膜运输 运输 膜运输
背景情况:
- 人类ATP结合盒载体子家族B6 (ABCB6) 是一种线粒体载体.
- 在ABCB6中,它促进了胺生物合成的氨酸转位.
- 保存的W546残留物通过π堆叠稳定了载体的封闭形状.
研究的目的:
- 研究ABCB6.6中W546A突变的结构和功能影响.
- 阐明W546在ABCB6形态动力学和基质运输中的作用.
- 为了比较洗剂微粒中的ABCB6行为与纳米磁盘.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定ABCB6.6的结构.
- 分析了W546A突变体在洗剂小粒和纳米盘中.
- 研究了形态动力学和基质结合相互作用.
主要成果:
- W546A突变将洗剂净化的ABCB6捕获到面向外的状态.
- 在纳米光盘中,脂与ABCB6相互作用,弥补W546的缺失.
- 这种相互作用促进了正常的形状过渡和ATP水解.
- 面向外的形状导致基质排斥和结合亲和力降低.
结论:
- W546残留物对于保持ABCB6的结构稳定性和功能至关重要.
- 膜环境,特别是纳米光盘中的脂,显著影响了ABCB6的动态.
- 该研究提供了对ABCB6-介导基质转位及其调节的见解.
相关概念视频
ABC Transporters: Exporter
4.4K
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...
4.4K
ABC Transporters: Importer
2.8K
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:
2.8K
Export of Misfolded Proteins out of the ER
3.6K
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...
3.6K
Membrane Asymmetry Regulating Transporters
4.5K
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...
4.5K
Carrier-Mediated Transport
460
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...
460
Structure of Porins
3.0K
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
3.0K


