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Conjugated Proteins02:50

Conjugated Proteins

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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...
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Viral Structure00:56

Viral Structure

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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.
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Structure of Cadherins01:25

Structure of Cadherins

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The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This...
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Leaky Scanning02:28

Leaky Scanning

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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...
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Structural Protein Function01:56

Structural Protein Function

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Structural Protein Function01:56

Structural Protein Function

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Structural proteins are a category of proteins responsible for functions ranging from cell shape and movement to providing support to major structures such as bones, cartilage, hair, and muscles. This group includes proteins such as collagen, actin, myosin, and keratin.
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity.  In bones and teeth, it mineralizes to...
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Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting
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ヒトACE2を用いたSARS-CoV-2の構造と機能の基礎

Qihui Wang1, Yanfang Zhang2, Lili Wu3

  • 1CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Cell
|April 11, 2020
PubMed
まとめ

SARS-CoV-2のスパイクタンパク質は,鍵となる残留物の変化により,より高い親和性でヒトACE2と結合する. SARS-CoVに対して有効な抗体は,SARS-CoV-2と結合せず,ウイルスの違いを強調しています.

キーワード:
ACE2 についてCTDSARS-CoV-2についてクリスタル構造免疫性についてレセプター受容体結合領域

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科学分野:

  • ウイルス学
  • 構造生物学
  • 免疫学

背景:

  • 新型コロナウイルス (SARS-CoV-2) が出現し,世界的な健康問題を引き起こした.
  • アンジオテンシン変換酵素2 (ACE2) は,SARS-CoV-2のエントリー受容体として特定されています.
  • SARS-CoV-2とACE2の相互作用を理解することは,治療開発にとって極めて重要です.

研究 の 目的:

  • SARS-CoV-2 C末端領域 (CTD) のヒト ACE2 (hACE2) に結合するスパイクタンパク質の結晶構造を決定する.
  • SARS-CoV-2がHACE2に結合する分子基盤を明らかにし,それをSARS-CoVと比較する.
  • SARS-CoVとSARS-CoV-2のスパイクタンパク質の抗原的差異を調査する.

主な方法:

  • SARS-CoV-2 CTD-hACE2複合体の構造を取得するために,X線結晶学を用いた.
  • 構造分析は,主要相互作用と残留物の違いを特定するために,結合インターフェースに焦点を当てた.
  • SARS-CoV スパイクタンパク質に対するモノクローナルおよびポリクローナル抗体を用いて抗体結合測定を行った.

主要な成果:

  • 結晶構造は,SARS-CoVに類似する hACE2結合モードを明らかにしたが,SARS-CoV-2-CTDにおける主要な残基置換がある.
  • これらの置換は,SARS-CoVと比較して,SARS-CoV-2とHACE2のわずかに強い相互作用とより高い結合親和性をもたらします.
  • SARS-CoVのスパイクタンパク質/受容体結合ドメイン (RBD) に対するネズミの抗体は,SARS-CoV-2のスパイクタンパク質と相互作用せず,異なる抗原性を示した.

結論:

  • 構造と結合に関するデータは,SARS-CoV-2の強化された受容体結合に関する洞察を提供します.
  • 抗原性の差異により,SARS-CoVに対する既存の抗体はSARS-CoV-2に対して効果的ではない可能性があります.
  • これらの発見は,ウイルス病原性を理解し,SARS-CoV-2に対する標的治療戦略を開発するために不可欠です.