尼曼-皮克C1蛋白的跨膜分子活动
J P Davies1, F W Chen, Y A Ioannou
1Department of Human Genetics, Box 1498, The Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
Science (New York, N.Y.)
|December 23, 2000
概括
尼曼-皮克C1 (NPC1) 蛋白质作为一个跨膜外流,利用质子动力从细胞中去除物质. 这一发现确定NPC1是RND透酶家族的真核细胞成员.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 尼曼-皮克C1 (NPC1) 疾病涉及溶酶体胆固醇积累和破坏细胞胆固醇恒温.
- 在细胞运输中NPC1蛋白的精确功能仍然不完全理解.
研究的目的:
- 研究NPC1蛋白在细胞运输机制中的功能作用.
- 为了确定NPC1是否与已知的运输蛋白家族表现出同质性.
- 阐明NPC1影响胆固醇平衡的机制.
主要方法:
- 对NPC1蛋白序列与 prokaryotic permease家族进行比较分析,特别是抵抗结节分裂 (RND) 家族.
- 在正常和NPC1缺陷纤维细胞中进行阿克里夫拉负荷研究,以评估NPC1在物质流量中的作用.
- 在大肠杆菌中NPC1的异质表达,以评估其对各种基质的运输能力.
主要成果:
- 有证据表明,NPC1蛋白与 prokaryotic RND permeases 具有同质性,这表明它可能作为跨膜排泄发挥作用.
- 缺乏NPC1的纤维细胞表现出失效的阿克里夫拉去除,这表明NPC1参与了使用质子动力在流出过程中的作用.
- 表达NPC1的大肠杆菌促进了阿克里夫拉的运输和油酸的运输,但不促进胆固醇或胆固醇-油酸盐的运输.
结论:
- 该NPC1蛋白质作为RND透酶家族的真核细胞成员起作用.
- NPC1充当了跨膜外流,有助于细胞胆固醇平衡.
- 了解NPC1的运输功能,可以了解尼曼-皮克C1疾病的机制.
相关概念视频
01:47Primary 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...
01:29Primary 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...
01:27ATP 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...
01:34ATP 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...
01:30ATP 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...
01:29Primary 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...