一种古老蛋白质的晶体结构:通过形态表达的进化
Eric A Ortlund1, Jamie T Bridgham, Matthew R Redinbo
1Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599, USA.
概括
研究人员使一种古老的蛋白质前体复活到脊椎动物的葡萄糖皮质体 (GR) 和矿物质皮质体 (MR) 受体. 结构分析揭示了推动GR的关键突变.
科学领域:
- 进化生物学是进化的生物学.
- 结构生物学是结构生物学.
- 分子进化的分子进化.
背景情况:
- 了解蛋白质进化对于破译功能多样化至关重要.
- 激素受体的进化途径,如葡萄糖皮质体 (GR) 和矿物质皮质体 (MR) 受体,仍然在很大程度上是未知的.
- 对祖先蛋白质结构的直接证据很少,限制了对功能过渡的洞察力.
研究的目的:
- 阐明新的蛋白质功能进化背后的结构机制.
- 重建和分析脊椎动物GR和MR受体的祖先前体.
- 为了确定特定的历史突变,负责GR从MR类祖先的分歧.
主要方法:
- 一个4亿5千万年前的祖先蛋白质的复活.
- 进行X射线晶体学以确定祖先蛋白质的结构.
- 综合结构,遗传学和功能分析来追踪进化变化.
主要成果:
- 获得了复活的祖先GR/MR前体的晶体结构.
- 确定了特定的历史突变,重述了GR激素特异性的演变.
- 这些突变改变了受体-连接体和蛋白内相互作用,由表皮和允许突变驱动.
结论:
- 从MR类祖先的GR激素特异性的演变涉及特定的残留物重新定位.
- 皮质相互作用和"宽容性"突变对于使功能转变成为可能至关重要.
- 这项研究为激素受体的进化轨迹提供了直接的结构证据.
相关概念视频
Protein Folding
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Folding
Overview
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...
Protein Organization
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence.
The primary structure of a protein is its amino acid sequence.
Protein Organization
Overview
Gene Duplication and Divergence
The seminal work of Ohno in 1970 popularized the idea of gene duplication and divergence. DNA sequence comparison studies reveal that a large portion of the genes in bacteria, archaebacteria, and eukaryotes was generated by gene duplication and divergence, indicating its critical role in evolution.
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are characterized.
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are characterized.


