Structural basis for SARS-CoV-2 envelope protein recognition of human cell junction protein PALS1.
Amino Acid Sequence
Coronavirus Envelope Proteins
/ chemistry
Cryoelectron Microscopy
Humans
Intercellular Junctions
/ metabolism
Membrane Proteins
/ metabolism
Nucleoside-Phosphate Kinase
/ metabolism
Protein Domains
SARS-CoV-2
/ physiology
Structural Homology, Protein
Structure-Activity Relationship
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 06 2021
08 06 2021
Historique:
received:
19
02
2021
accepted:
30
04
2021
entrez:
9
6
2021
pubmed:
10
6
2021
medline:
16
6
2021
Statut:
epublish
Résumé
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has created global health and economic emergencies. SARS-CoV-2 viruses promote their own spread and virulence by hijacking human proteins, which occurs through viral protein recognition of human targets. To understand the structural basis for SARS-CoV-2 viral-host protein recognition, here we use cryo-electron microscopy (cryo-EM) to determine a complex structure of the human cell junction protein PALS1 and SARS-CoV-2 viral envelope (E) protein. Our reported structure shows that the E protein C-terminal DLLV motif recognizes a pocket formed exclusively by hydrophobic residues from the PDZ and SH3 domains of PALS1. Our structural analysis provides an explanation for the observation that the viral E protein recruits PALS1 from lung epithelial cell junctions. In addition, our structure provides novel targets for peptide- and small-molecule inhibitors that could block the PALS1-E interactions to reduce E-mediated virulence.
Identifiants
pubmed: 34103506
doi: 10.1038/s41467-021-23533-x
pii: 10.1038/s41467-021-23533-x
pmc: PMC8187709
doi:
Substances chimiques
Coronavirus Envelope Proteins
0
Membrane Proteins
0
envelope protein, SARS-CoV-2
0
Nucleoside-Phosphate Kinase
EC 2.7.4.4
MPP5 protein, human
EC 2.7.4.8
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
3433Subventions
Organisme : NIGMS NIH HHS
ID : P30 GM133893
Pays : United States
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