ディストログリカンの機能には,XylosylとGlucuronyltransferaseの活動が非常に大きいことが必要です
Kei-ichiro Inamori1, Takako Yoshida-Moriguchi, Yuji Hara
1Howard Hughes Medical Institute, Department of Molecular Physiology and Biophysics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, 4283 Carver Biomedical Research Building, 285 Newton Road, Iowa City, IA 52242-1101, USA.
まとめ
アセチルグルコサミニルトランスフェラーゼのような (LARGE) 酵素はアルファ-ディストログリカン (α-DG) を改変し,細胞外マトリックスリンガンドと結合することを可能にします. この二機能酵素は,α-DGの適切な機能に不可欠であり,筋縮の治療に重要な役割を果たす可能性があります.
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.
- 遺伝学 遺伝学とは
背景:
- アルファ-ディストログリカン (α-DG) の翻訳後の改変は,細胞外マトリックス (ECM) 受容体としての機能に不可欠です.
- アセチルグルコサミニルトランスフェラーゼ (LARGE) のような遺伝子の変異は,先天性筋縮症と脳異常に関連しています.
- LARGEの正確な酵素機能は,まだ完全に理解されていません.
研究 の 目的:
- LARGE酵素の正確な生化学的機能を明らかにするために.
- LARGEがα-DGを改変してECMの相互作用を促進する方法を理解する.
主な方法:
- LARGEのグリコシルトランスファーゼ活性を決定する酵素測定法.
- LARGEによるα-DG変異の生化学分析.
- LARGEの改変後にECMリガンドへのα-DG結合の評価.
主要な成果:
- LARGEは,キシロシルトランスフェラーゼとグルキュロニルトランスフェラーゼの両方の機能を兼ね備えた,二機能性グリコシルトランスフェラーゼ活性を示す.
- LARGEは,α-DG上で[-3-キシロース-α1,3-グルキュロン酸-β1-]の繰り返し単位を合成する.
- この改変により,α-DGはラミニン-Gドメインを含むECMリガンドと結合することができる.
結論:
- LARGEは,特定のグリコシド単位の合成を通じて,ECM結合のためのα-DGを改変する重要な酵素として作用します.
- LARGEの機能を理解することで,先天性筋ジストロフィーの病原性についての洞察が得られます.
- この発見は,LARGE媒介型グリコシライゼーションを標的とした治療戦略の道を開く.
関連する概念動画
Oligosaccharide Assembly
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
Proteoglycans
Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
Protein Folding Quality Check in the RER
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
Protein Glycosylation
Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
Glycosylation occurs in...
Glycosaminoglycans
Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are long and linear polymers comprising of specific repeating disaccharides - the amino sugar that can be N-acetylglucosamine or N-acetylgalactosamine, and a uronic acid that is usually glucuronic acid or iduronic acid.
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...
Glycocalyx and its Functions
The glycocalyx is a carbohydrate-rich, fuzzy-appearing layer on the outer surface of the cell membrane. It is highly hydrophilic, because of this it attracts large amounts of water to the cell's surface. This aids the cell's interaction with the watery environment and also helps it to obtain substances dissolved in the water. It is also important for cell identification, self/non-self determination, and embryonic development and is used in cell-to-cell attachments to form tissues.
Components of...
Components of...

