SARS-CoV-2 スパイク・グリコタンパク質の構造,機能,抗原性
Alexandra C Walls1, Young-Jun Park1, M Alejandra Tortorici2
1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Cell
|March 11, 2020
まとめ
SARS-CoV-2のスパイクタンパク質は,SARS-CoVに似たACE2を用いて細胞に入ります. SARS-CoV-2におけるユニークなフーリン分裂部位
科学分野:
- ウイルス学
- 構造生物学
- 免疫学
背景:
- 深刻な急性呼吸器症候群コロナウイルス2型 (SARS-CoV-2) が発生し,世界的な健康に影響を及ぼしました.
- コロナウイルスのスパイク (S) のグリコプロテインは,ウイルスの侵入に不可欠であり,抗体を中和する主な標的である.
- SARS-CoV-2 Sタンパク質の構造と機能を理解することは,医療対策の開発に不可欠です.
研究 の 目的:
- SARS-CoV-2の細胞侵入メカニズムを調査する.
- SARS-CoV-2 Sグリコタンパク質の構造的特徴を特徴づける.
- Sタンパク質を標的とした治療戦略を探求する.
主な方法:
- SARS-CoV-2 Sタンパク質とヒトのアンジオテンシン変換酵素2 (ACE2) の相互作用の分析.
- SARS-CoV-2 S エクトドメイントリマーの冷凍電子顕微鏡 (cryo-EM) 構造の決定.
- SARS-CoV-2 S媒介ウイルスの侵入に対する抗体中和の評価.
主要な成果:
- SARS-CoV-2 Sは,ACE2を細胞への侵入に利用し,SARS-CoV Sと同様にヒトのACE2に結合する afinityを持っています.
- SARS-CoV-2 SのS1/S2サブユニット境界で新しいフーリン分裂部位が特定され,他のコロナウイルスと区別されました.
- Cryo-EM構造は,SARS-CoV-2 Sタンパク質のトリメリックエクトドメインを明らかにした.
- SARS-CoV Sに対するネズミのポリクローン抗体は,SARS-CoV-2 S媒介細胞の侵入を強力に抑制することを示した.
結論:
- この発見は,SARS-CoV-2に対するワクチンおよび阻害剤の設計のための構造的な青写真を提供します.
- フーリン分裂部位の存在は,SARS-CoV-2の効率的な拡散に寄与する可能性があります.
- 保存されたSエピトープを標的とするクロス中和抗体は,治療介入とワクチン接種戦略の有望な道を示しています.
さらに関連する動画
関連する概念動画
Conjugated Proteins
26.0K
Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
26.0K
Viral Structure
73.5K
Viruses are extraordinarily diverse in shape and size, but they all have several structural features in common. All viruses have a core that contains a DNA- or RNA-based genome. The core is surrounded by a protective coat of proteins called the capsid. The capsid is composed of subunits called capsomeres. The capsid and genome-containing core are together known as the nucleocapsid.
73.5K
Leaky Scanning
5.5K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.5K
Glycocalyx and its Functions
7.5K
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.
7.5K
Protein Glycosylation
9.0K
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...
9.0K
Antibody Structure
65.1K
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
65.1K


