胆盐出口的非正规核酸结合部位1为输送器的正常功能而优化
Imran Sohail1,2, Mahmood Ul Hassan2,3, Diethart Schmid4
1Department of Zoology, Government College University Lahore, Lahore, Pakistan.
Cell biology international
|February 8, 2024
概括
胆盐出口 (ABCB11/BSEP) 的突变会影响其功能. 核酸结合位点1中的特定残留物变化减少了运输活性,突出显示了这些相互作用对BSEP功能的重要性.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 肝病学 肝病学是一种肝病学.
背景情况:
- 胆盐输出 (ABCB11/BSEP) 对于将胆盐从肝细胞输出至关重要.
- 序列分析显示,与其他ABCB亚家族成员相比,ABCB11的核酸结合部位1 (NBS1) 中存在独特的残留物.
- 以前的研究表明,改变所有四种独特的残留物 (四重突变) 显著损害了BSEP的运输活动.
研究的目的:
- 研究ABCB11 NBS1.1.中的特定突变的功能影响.
- 通过改变关键残留物来产生和描述ABCB11的双重和三重突变.
主要方法:
- 用局部定向的突变发生法来创造ABCB11的双 (R1221G/E1223Q) 和三 (E502S/R1221G/E1223Q) 突变.
- 评估了野生类型和突变的BSEP蛋白质的运输活动.
主要成果:
- 双重突变者保留了80%的野生型BSEP运输活动.
- 三重突变体表现出60%的野生型BSEP运输活动.
- 这些发现表明突变对BSEP功能具有剂量依赖的影响.
结论:
- 在ABCB11的NBS1中发生的特定突变,特别是在签名序列和Q循环中,会影响胆汁盐的运输.
- 在ABC蛋白中,复杂的相互作用网络对于维持适当的传送器功能至关重要.
- 了解这些相互作用可以为与BSEP功能障碍相关的肝脏疾病的治疗策略提供信息.
更多相关视频
12:07Chemical Modification of the Tryptophan Residue in a Recombinant Ca2+-ATPase N-domain for Studying Tryptophan-ANS FRET
Published on: October 9, 2021
3.4K
13:16Characterization of Membrane Transporters by Heterologous Expression in E. coli and Production of Membrane Vesicles
Published on: December 31, 2019
9.3K
相关概念视频
Ligand Binding and Linkage
4.8K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
4.8K
Conserved Binding Sites
4.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.2K
Allosteric Proteins-ATCase
5.7K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.7K
Ligand Binding Sites
12.8K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
12.8K
ABC Transporters: Exporter
4.3K
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...
4.3K
Nuclear Export
3.6K
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.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
3.6K
