SARS-CoV-2のスパイクタンパク質のロックされた構造のフリー脂肪酸結合ポケット

Christine Toelzer^1,2, Kapil Gupta^1,2, Sathish K N Yadav^1,2

¹School of Biochemistry, University of Bristol, 1 Tankard's Close, Bristol BS8 1TD, UK.

Science (New York, N.Y.)

|September 22, 2020

まとめ

リノール酸 (LA) はSARS-CoV-2のスパイクタンパク質と結合し,その構造を安定させ,ACE2の相互作用を減少させます. この発見は,COVID-19に対する新しい治療戦略につながる可能性があります.

科学分野:

構造生物学
ウイルス学
生物化学

背景:

SARS-CoV-2によって引き起こされるコロナウイルス病 2019 (COVID-19) は,世界的な健康危機である.
SARS-CoV-2のメカニズムを理解することは,効果的な治療薬の開発に不可欠です.
スパイク (S) グリコプロテインはウイルスの感染性と病理性を駆動する.

研究の目的:

SARS-CoV-2の感染性の構造的基礎を解明する.
Sグリコタンパク質の機能における自由脂肪酸の役割を調査する.
COVID-19の潜在的な治療標的を特定する.

主な方法:

クリオ電子顕微鏡で 2.85 アングストロムの解像度で
SARS-CoV-2 Sグリコタンパク質の構造分析
ACE2の相互作用とウイルスの複製を評価する in vitro 試験.
ヒト細胞におけるリノール酸の補充

主要な成果:

SARS-CoV-2 Sグリコプロテインにはリノール酸 (LA) の結合ポケットが3つあります.
LA結合は,Sグリコタンパク質を"ロックされた"形状で安定させる.
この形状は,アニオテンシン変換酵素2 (ACE2) との相互作用を in vitro で減少させる.
LAはレムデシビルと連携して,ヒト細胞におけるSARS-CoV-2の複製を抑制する.
同様のLA結合ポケットはSARS-CoVとMERS-CoVに示唆されています.

結論:

リノール酸はSARS-CoV-2のスパイクタンパク質と直接相互作用する.
LA結合は,ウイルスの侵入と安定性に影響を与える新しいメカニズムを表しています.
LA結合をターゲットにすることは,COVID-19および関連するコロナウイルスに対する潜在的な治療戦略を提供します.

さらに関連する動画

07:53

A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation

Published on: January 9, 2019

33.6K

08:40

Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting

Published on: March 1, 2019

59.5K

関連する概念動画

01:49

Conserved Binding Sites

4.9K

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...

4.9K

01:49

Conserved Binding Sites

1.9K

01:32

Lipids as Anchors

6.9K

In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...

6.9K

02:50

Conjugated Proteins

25.0K

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...

25.0K

02:40

Ligand Binding Sites

14.6K

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...

Protein Folding