タンパク質フォスファタゼ2Aの脱メチル化と不活性化の構造的メカニズム
1Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Princeton, NJ 08544, USA.
Cell
|April 9, 2008
まとめ
タンパク質フォスファタゼ2A (PP2A) の脱メチル化はPME-1によって調節される. 結晶構造は,PME-1が活性化し,PP2Aは必須のマンガンイオンを除去することによって無活性化されます.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 酵素学 酵素学とは
背景:
- タンパク質フォスファタゼ2A (PP2A) は,多数の細胞プロセスに不可欠です.
- リバーシブルカルボキシルメチル化により,PP2Aの触媒サブユニット機能が調節される.
- メチルエステラーゼであるPME-1は,PP2Aの脱メチル化と負の調節を媒介する.
研究 の 目的:
- PP2A規則におけるPME-1機能の構造的メカニズムを解明する.
- PME-1がPP2Aの活動とどのように相互作用し,変更するかを理解する.
主な方法:
- X線結晶学を用いて,単独でPME-1とPP2Aとの複合体の構造を決定した.
- 構造分析は,活性部位の相互作用と形状の変化に焦点を当てました.
主要な成果:
- PME-1は,PP2A活性部位に直接結合する.
- この相互作用がPME-1を活性化させ,好ましい触媒トライアード構成を誘導する.
- PME-1は活性部位から必須のマンガンイオンを排出するので,PP2Aは非活性化されます.
結論:
- PME-1は,PP2Aの規制において二重な役割を果たしている.
- PME-1は,PP2Aの活性化,メチル化状態,ホロ酵素組成を制御しています.
- 構造的な洞察は,セルラーPP2A調節におけるPME-1の機能のメカニズム的基礎を提供します.
関連する概念動画
01:02Phosphorylation
44.8K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
44.8K
02:54Protein Kinases and Phosphatases
12.2K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
12.2K
02:04Covalently Linked Protein Regulators
8.2K
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....
8.2K
01:22Amplifying Signals via Enzymatic Cascade
15.3K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
15.3K
01:16Calmodulin-dependent Signaling
5.0K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.0K
01:17Phase II Reactions: Methylation Reactions
921
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
921