複雑でペプチドのない膜タンパク質結合ドメインの結晶構造:PDZによるペプチド認識の分子基礎
1Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, New York, NY 10021, USA.
Cell
|June 28, 1996
まとめ
モジュール式PDZドメインは,タンパク質C端に結合し,イオンチャネルをクラスタリングします. 構造分析は特定の相互作用を明らかにし,PSD-95 PDZドメインがターゲット配列を認識する方法を説明します.
科学分野:
- 構造生物学 構造生物学とは
- 分子生物学は分子生物学である.
- 神経科学は神経科学である.
背景:
- PDZドメインは,細胞結合タンパク質における重要なモジュラー相互作用モジュールである.
- タンパク質とタンパク質の相互作用を媒介し,しばしばC端末結合を伴う.
- PDZドメインは,イオンチャネルを含む膜タンパク質の組織化に役割を果たします.
研究 の 目的:
- PSD-95 PDZドメインのX線結晶構造を決定する.
- PDZドメインによるペプチドリガンド認識の構造的基礎を解明する.
- PDZドメインが細胞の交差点でのタンパク質のクラスタリングをどのように媒介するかを理解する.
主な方法:
- 構造を決定するために,X線結晶学を用いた.
- 高解像度 (1.8および2.3アンストーム) のデータを収集した.
- ペプチドリガンドの有無を問わず複雑な構造を分析した.
主要な成果:
- 構造は,PDZドメインと4つの残基C端ペプチドの間の反並列主鎖相互作用を明らかにします.
- Gly-Leu-Gly-Pheループとアルギニン側鎖は,ペプチドの末端カルボキシラート群を認識するために重要である.
- PDZドメイン内の防水ポケットは,C端のコンセンサス配列に選択性を授与する.
結論:
- この研究は,PDZドメイン-ペプチド相互作用に関する詳細な構造的洞察を提供します.
- これらの発見は,PDZドメインによるC端末配列の選択的認識の分子基盤を説明します.
- この構造的な理解は,PDZドメイン媒介シグナル伝達経路のモデュレータの設計に役立つ.
さらに関連する動画
13:02Production, Crystallization, and Structure Determination of the IKK-binding Domain of NEMO
Published on: December 28, 2019
06:50Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions
Published on: January 26, 2024
関連する概念動画
Conservation of Protein Domains Over Different Proteins
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
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...
Membrane Domains
The membrane domains concentrate specific lipids and proteins at one place within the membrane, which helps in cell signaling, adhesion, and other critical cellular processes. These domains can differ in size, composition, function, and lifespan.
Protein Domains
The membrane comprises a group of distinct proteins responsible for carrying out a cell's specific function. For example, the plasma membrane of the human sperm, or a single germ cell, contains a unique set of proteins in the anterior...
Protein Domains
The membrane comprises a group of distinct proteins responsible for carrying out a cell's specific function. For example, the plasma membrane of the human sperm, or a single germ cell, contains a unique set of proteins in the anterior...
Multi-pass Transmembrane Proteins and β-barrels
In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
Mechanisms of Membrane Domain Formation
Different physical properties of lipids and proteins allow them to localize and form distinct islands or domains in the membrane. Some membrane domains are formed due to protein-protein interactions, whereas others are formed due to the presence of specific lipids such as sphingolipids and sterols—for example, large proteins, such as bacteriorhodopsin, aggregate and create distinct domains.
Another mechanism for membrane domain formation involves membrane proteins interacting with cytoskeletal...
Another mechanism for membrane domain formation involves membrane proteins interacting with cytoskeletal...
Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
