構造,基板認識およびヒアルロナン合成の開始
Finn P Maloney1, Jeremi Kuklewicz1, Robin A Corey2
1Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA, USA.
Nature
|March 31, 2022
まとめ
研究者らは,細胞外マトリックス成分であるヒアルロナンの合成におけるヒアルロナン合成酵素 (HAS) のメカニズムを明らかにした. この研究では,HASが基質を選択し,ポリマーを形成する方法を詳細に説明し,グリコサミノグリカン生物合成の洞察を提供します.
科学分野:
- 生物化学
- 構造生物学
- 細胞外マトリックス生物学
背景:
- hialuronan (HA) は,重要な生理学的プロセスに関与する重要な細胞外マトリックスヘテロポリサッカライドです.
- ハイアルーロン合成酵素 (HAS) は,活性化糖の前駆体を使用して,膜に埋め込まれたプロセスを介してHAを合成します.
研究 の 目的:
- HASによるヒアルロナンの合成の分子メカニズムを解明する.
- HAバイオシンセシス中の基板選択,ポリメリゼーション,および製品転位に関する構造的洞察を提供すること.
主な方法:
- クリオ電子顕微鏡 (cryo-EM) で,ウイルスのHAS同類体の構造を決定する.
- 酵素の活性を調べるための生化学分析
- 基板相互作用とポリメリゼーションをモデル化するための分子動力学シミュレーション.
主要な成果:
- 5つの冷凍-EM構造は,基板結合とポリマー合成の開始の様々な段階でHASを捕獲しました.
- この研究では,HASが基質を選択し,反応をプライムし,トランスメブランチャネルを形成し,交互のポリメリゼーションを確保する方法が明らかにされています.
- ハイアルロナンの形成とHAS孔を通じた転移の詳細なモデルが提案されています.
結論:
- 重要なグリコスアミノグリカンであるヒアルロナンの生物合成に関する包括的な理解が得られました.
- この研究は,ヒアルロナン合成酵素の構造-機能関係に関する洞察を提供します.
- この研究は,酸性細胞外ヘテロポリサッカリドの形成を明らかにした.
関連する概念動画
Oligosaccharide Assembly
3.0K
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...
3.0K
Lysosomal Hydrolases
3.9K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.9K
Hydrolysis
117.9K
Overview
Hydrolysis is a chemical reaction in which the addition of water breaks down a polymer into its simpler monomer units. For example, peptides break into amino acids, carbohydrates into simple sugars, and DNA into nucleotides. Enzymes often facilitate these processes.
Hydrolysis Reverses Dehydration Synthesis
Complex carbohydrates can be broken down by breaking the bonds between individual sugar units. The reaction breaks a glycosidic bond as water is added to the compound. The...
Hydrolysis is a chemical reaction in which the addition of water breaks down a polymer into its simpler monomer units. For example, peptides break into amino acids, carbohydrates into simple sugars, and DNA into nucleotides. Enzymes often facilitate these processes.
Hydrolysis Reverses Dehydration Synthesis
Complex carbohydrates can be broken down by breaking the bonds between individual sugar units. The reaction breaks a glycosidic bond as water is added to the compound. The...
117.9K
Role of Microtubules in Cell Wall Deposition
2.6K
Microtubules are small hollow tubes in eukaryotic cells. The cell wall microtubules are polymerized dimers of two globular proteins, α-tubulin and β-tubulin, two globular proteins. With a diameter of about 25 nm, microtubules are the widest components of the cytoskeleton. They help the cell resist compression and provide a track along which vesicles move through the cell or pull replicated chromosomes to opposite ends of a dividing cell. Microtubules go through quick cycles of...
2.6K
Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
8.7K
The rate of acid-catalyzed hydration of alkenes depends on the alkene's structure, as the presence of alkyl substituents at the double bond can significantly influence the rate.
8.7K
Mechanism of Lamellipodia Formation
2.8K
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
2.8K


