DNAアプタマー-タンパク質の相互作用を用いたタンパク質活動のプログラム可能で自律的な調節のための論理的な分子回路
1Department of Chemistry, Center for Research at the Bio/Nano Interface, Shands Cancer Center and UF Genetics Institute, University of Florida, Gainesville, Florida 32611-7200, USA.
Journal of the American Chemical Society
|December 1, 2012
まとめ
研究者らは,タンパク質の活性に対するプログラム可能な制御のための新しいDNA-タンパク質相互作用回路を開発した. この合成生化学回路は,パーソナライズド医療における潜在的な応用のために,自律的で自己持続的な操作を提供します.
科学分野:
- バイオケミカルエンジニアリング
- 合成生物学 合成生物学とは
- 分子工学は分子工学である.
背景:
- 人工生化学回路は,電気回路と同様の,生物工学の重要な構成要素として想定されています.
- これまでの合成生化学回路は,主にDNAのハイブリッド化と鎖移転反応に依存していた.
- 細胞のない合成生化学回路は,多種多様なin vitro化学と生物分子機能を制御するための強度と可能性を備えています.
研究 の 目的:
- 精密な値制御によるDNAとタンパク質の相互作用に基づく最初の論理回路を記述する.
- タンパク質の活性に関する自律的,自立的,プログラム可能な操作を in vitro で可能にする.
- 酵素環境を感知し,特定の分子トリガーに基づいて阻害物質を放出するための新しいアプローチを実証する.
主な方法:
- DNAとタンパク質の相互作用を利用した新しい論理回路の開発.
- 自律回路操作のための正確な値制御の実装.
- トロンビン濃度を感知し,凝固阻害剤を放出する分子回路の能力を実証.
主要な成果:
- この研究は,正確な値制御を備えた最初のDNA-タンパク質相互作用ベースの論理回路を提示しています.
- 開発された回路は,タンパク質活動の自律的,自立し,プログラム可能な操作を in vitro で可能にします.
- 原則証明のデモでは,トロンビン濃度に基づくプログラム可能で自律的な調節のための回路の能力を示しました.
結論:
- この新しいDNA生化学回路は,以前の設計よりも大きな進歩を示しています.
- 回路の調節可能な調節,モジュラリティ,およびターゲット特異性は,将来のアプリケーションの道を開く.
- 将来の潜在的な応用には,パーソナライズされた医療のためのスマートな薬物投与システムの開発が含まれます.
関連する概念動画
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
01:19Allosteric 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,...
02:26Protein Networks
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
01:57Protein Complexes with Interchangeable Parts
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
00:49Ligand 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...
03:06From DNA to Protein
The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...