高级真核多胺管结合蛋白的独特结合特异性和功能
R Singh1, J Valcárcel, M R Green
1Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester 01605, USA.
概括
聚皮里米丁管结合蛋白 (PTB) 和其他拼接因子在拼接部位附近识别出不同的序列. PTB通过结合到特定部位来选择性地抑制替代拼接,从而影响基因表达.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 在RNA分离过程中.
背景情况:
- 在3'拼接部位附近的多聚胺通道 (Py-tract) 对于真核生物的mRNA前拼接至关重要.
- 一些蛋白质,包括U2AF65,Sex-lethal (Sxl) 和聚胺系结合蛋白 (PTB),与Py-tract相互作用.
- 之前,在拼接调节中,PTB的精确功能和序列偏好是未知的.
研究的目的:
- 为了研究拼接因子U2AF65,Sxl和PTB的独特序列偏好.
- 阐明PTB在替代拼接法规中的作用.
主要方法:
- 代体内遗传选择被用于确定蛋白质特异性序列偏好.
- 对天然甲状动物Py-tracts和替代拼接前mRNAs的分析.
主要成果:
- U2AF65结合于类似于自然甲基动物Py-tracts的富含尿素的序列.
- Sxl 识别了一个高度特定的共识序列,解释其监管作用.
- PTB与负调节的替代拼接前mRNAs中发现的独特的共识序列结合.
- PTB被证明可以选择性地抑制含有其结合部位的3'拼接部位.
结论:
- 拼接因子对Py-tract识别具有明显的序列特异性.
- 通过抑制特定的3'拼接位,PTB在替代拼接中发挥着重要作用.
- 了解这些相互作用为通过替代拼接来调节基因表达提供了洞察力.
相关概念视频
Conserved Binding Sites
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 analyses the...
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 analyses the...
Ligand Binding and Linkage
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 the...
Eukaryotic RNA Polymerases
RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal, and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.
All three eukaryotic RNAPs require specific transcription factors, of which the...
All three eukaryotic RNAPs require specific transcription factors, of which the...
Transfer RNA Synthesis
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Allosteric Proteins-ATCase
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 pathway,...
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 pathway,...
Single-Strand DNA Binding Proteins
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...


