对于真核细胞/质子交换机交替访问的结构基础
Andrew B Waight1, Bjørn Panyella Pedersen, Avner Schlessinger
1Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA.
Nature
|May 21, 2013
概括
研究人员确定了/质子 (Ca2+/H+) 交换器Vcx1的晶体结构,揭示了它与基质结合的,面向细胞质的形状. 这为Ca2+:cation (CaCA) 超级家族提供了第一个结构洞察力.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 细胞生理学 细胞生理学
背景情况:
- 细胞 (Ca2+) 调节对于信号通路至关重要,涉及器官结合和快速细胞溶液释放.
- 该Ca2+:cation (CaCA) 超级家族,包括Na+/Ca2+ (NCX) 和Ca2+/H+ (CAX) 反载体,对于恢复Ca2+稳态至关重要.
- 哺乳动物NCX蛋白 (SLC8,SLC24家族) 调节肌肉,神经元和脏中的Ca2+;CAX家族成员在植物和真菌中保持Ca2+平衡.
研究的目的:
- 为了阐明CaCA超级家族未知的细胞质面向构造.
- 了解CaCA反载波器的投机运输机制.
- 为了确定Saccharomyces cerevisiae真空Ca2+/H+交换器 (Vcx1) 的高分辨率晶体结构.
主要方法:
- 确定了Saccharomyces cerevisiae Vcx1.1.的晶体结构
- 使用2.3 Å分辨率的X射线晶体学.
- 捕获的Vcx1在一个基质结合的,面向细胞质的 conformation.
主要成果:
- 在CaCA超级家族中,CAX家族成员 (Vcx1) 的第一个晶体结构.
- 揭示了CaCA超级家族的关键细胞质面向构造.
- 为一种新的交替接入机制提供结构基础,以促进高吞吐量Ca2+运输.
结论:
- 确定的Vcx1结构为CaCA超级家族的机制提供了关键的见解.
- 建立了一个结构基础,以了解这些反输送器如何实现高效的Ca2+运输.
- 新的交替访问机制解释了高通量Ca2+运输能力.
相关概念视频
Feedback Regulation of Calcium Concentration
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Primary Active Transport
In contrast to passive transport, active transport involves a substance being moved through membranes in a direction against its concentration or electrochemical gradient. There are two types of active transport: primary active transport and secondary active transport. Primary active transport utilizes chemical energy from ATP to drive protein pumps embedded in the cell membrane. With energy from ATP, the pumps transport ions against their electrochemical gradients—a direction they would not...
Primary Active Transport
In contrast to passive transport, active transport involves a substance being moved through membranes in a direction against its concentration or electrochemical gradient. There are two types of active transport: primary active transport and secondary active transport. Primary active transport utilizes chemical energy from ATP to drive protein pumps that are embedded in the cell membrane. With energy from ATP, the pumps transport ions against their electrochemical gradients—a direction they...
ATP Driven Pumps II: P-type Pumps
The P-type pumps are a large family of integral membrane transporter ATPases. They are divided into five major types based on substrate specificity, from I to V.
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
ATP Driven Pumps III: V-type Pumps
V-type pumps are ATP-driven pumps found in the vacuolar membranes of plants, yeast, endosomal and lysosomal membranes of animal cells, plasma membranes of a few specialized eukaryotic cells, and some prokaryotes. They are also known as the V1Vo-ATPase, that couple ATP hydrolysis to transport protons against a concentration gradient.
The peripheral or cytosolic V1 domain with eight subunits is involved in ATP hydrolysis. The integral or transmembrane V0 domain containing at least five subunits...
The peripheral or cytosolic V1 domain with eight subunits is involved in ATP hydrolysis. The integral or transmembrane V0 domain containing at least five subunits...
ATP Driven Pumps I: An Overview
ATP-driven pumps, also known as transport ATPases, are integral membrane proteins. They have binding sites for ATP located on the membrane's cytosolic side and the ion-conducting domain in the transmembrane region. These pumps use the free energy released from ATP hydrolysis to move the solutes across cell membranes against an electrochemical gradient.
There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and are...
There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and are...


