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Structure paper

TitleMolecular basis of specific viral RNA recognition and 5'-end capping by the Chikungunya virus nsP1.
Journal, issue, pagesCell Rep, Vol. 40, Issue 4, Page 111133, Year 2022
Publish dateJul 26, 2022
AuthorsKuo Zhang / Michelle Cheok Yien Law / Trinh Mai Nguyen / Yaw Bia Tan / Melissa Wirawan / Yee-Song Law / Lak Shin Jeong / Dahai Luo /
PubMed AbstractMany viruses encode RNA-modifying enzymes to edit the 5' end of viral RNA to mimic the cellular mRNA for effective protein translation, genome replication, and evasion of the host defense mechanisms. ...Many viruses encode RNA-modifying enzymes to edit the 5' end of viral RNA to mimic the cellular mRNA for effective protein translation, genome replication, and evasion of the host defense mechanisms. Alphavirus nsP1 synthesizes the 5' end Cap-0 structure of viral RNAs. However, the molecular basis of the capping process remains unclear. We determine high-resolution cryoelectron microscopy (cryo-EM) structures of Chikungunya virus nsP1 in complex with m7GTP/SAH, covalently attached m7GMP, and Cap-0 viral RNA. These structures reveal details of viral-RNA-capping reactions and uncover a sequence-specific virus RNA-recognition pattern that, in turn, regulates viral-RNA-capping efficiency to ensure optimal genome replication and subgenomic RNA transcription. This sequence-specific enzyme-RNA pairing is conserved across all alphaviruses.
External linksCell Rep / PubMed:35905713
MethodsEM (single particle)
Resolution2.18 - 2.62 Å
Structure data

31580

7fgg

EMDB-31580, PDB-7fgg:
Cryo-EM Structure of Chikungunya Virus Nonstructural Protein 1 with m7GTP
Method: EM (single particle) / Resolution: 2.19 Å

31581

7fgh

EMDB-31581, PDB-7fgh:
Cryo-EM Structure of Chikungunya Virus Nonstructural Protein 1 with m7GMP
Method: EM (single particle) / Resolution: 2.18 Å

31582

7fgi

EMDB-31582, PDB-7fgi:
Cryo-EM Structure of Chikungunya Virus Nonstructural Protein 1 with m7Gppp-AU
Method: EM (single particle) / Resolution: 2.51 Å

32914

7x01

EMDB-32914, PDB-7x01:
Cryo-EM Structure of Chikungunya Virus Nonstructural Protein 1 with inhibitor FHA
Method: EM (single particle) / Resolution: 2.62 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-SAH:
S-ADENOSYL-L-HOMOCYSTEINE / S-Adenosyl-L-homocysteine

ChemComp-MGP:
7-METHYL-GUANOSINE-5'-TRIPHOSPHATE

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER / Water

ChemComp-G7M:
N7-METHYL-GUANOSINE-5'-MONOPHOSPHATE

ChemComp-GTA:
P1-7-METHYLGUANOSINE-P3-ADENOSINE-5',5'-TRIPHOSPHATE

ChemComp-U:
URIDINE-5'-MONOPHOSPHATE / Uridine monophosphate

ChemComp-G:
GUANOSINE-5'-MONOPHOSPHATE / Guanosine monophosphate

ChemComp-7XQ:
(1R,2S,3S,4R,5R)-3-(6-aminopurin-9-yl)-4-fluoranyl-5-(2-hydroxyethyl)cyclopentane-1,2-diol

Source
  • chikungunya virus strain s27-african prototype
  • chikungunya virus (strain s27-african prototype)
KeywordsVIRAL PROTEIN / nonstructural protein / Chikungunya virus / RNA cap / replication / inhibitor

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