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Receptor-mediated Endocytosis01:20

Receptor-mediated Endocytosis

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Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
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Introduction to Virus01:28

Introduction to Virus

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Viruses are unique biological entities that blur the boundary between living and non-living systems. Although they lack cellular structure and metabolic processes, they can exhibit characteristics of life when infecting a host. Their defining feature is a nucleic acid core, composed of either DNA or RNA, encapsulated within a protein coat called a capsid. This simple structure allows them to invade host cells and use their machinery for replication efficiently.Viral Structure and...
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Viruses with RNA Genomes01:29

Viruses with RNA Genomes

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RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
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Viral Structure00:56

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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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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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Updated: Oct 20, 2025

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C型肝炎ウイルスの受容体結合と侵入に関する構造的洞察

Ashish Kumar1, Reafa A Hossain1, Samantha A Yost2

  • 1Structural Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Nature
|September 16, 2021
PubMed
まとめ

C型肝炎ウイルス (HCV) の侵入には,CD81受容体へのE2グリコタンパク質結合が含まれます. 低pHとCD81結合はE2の形状変化を誘導し,ウイルスの膜融合を促進する.

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A Protocol for Analyzing Hepatitis C Virus Replication
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Last Updated: Oct 20, 2025

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科学分野:

  • ウイルス学
  • 構造生物学
  • 細胞生物学

背景:

  • C型肝炎ウイルス (HCV) は慢性肝疾患,肝硬変,肝がんを引き起こし,世界中で7千万人以上が感染しています.
  • HCVエンベロープのグリコタンパク質E1とE2はウイルスの侵入を媒介するが,正確なメカニズムは不明である.
  • 中和抗体はしばしば,CD81受容体の大きな細胞外ループ (CD81-LEL) とのE2グリコタンパク質の相互作用を標的とする.

研究 の 目的:

  • HCVの侵入の構造的および分子的メカニズムを解明する.
  • HCV E2とCD81-LELの相互作用におけるpHとCD81結合の役割を調査する.
  • E2媒介膜融合の構造的基礎を決定する.

主な方法:

  • E2複合体の構造を決定するために,X線結晶学を用いた.
  • 主要なE2残留物に関する変異性研究が行われました.
  • リポソーム漂流試験は,E2と膜の相互作用を評価した.

主要な成果:

  • 低pHはCD81-LELのE2グリコタンパク質への結合を強化する.
  • 結晶構造は,CD81-LEL結合時にE2の形状の変化を明らかにし,残基418-422を移動させ,内部ループ (520-539) を拡張した.
  • 特定のE2残留物 (Tyr529, Trp531, Ile422) は,低pHとCD81-LELによって促進される膜相互作用に不可欠です.

結論:

  • 酸性化とCD81-LEL結合は,E2の形状変化を誘導する.
  • この形状の変化は,膜融合のためのE2をプライムし,HCVの侵入における重要なステップを表します.
  • この発見は,HCVと宿主細胞膜の相互作用の分子モデルを提供する.