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Structure paper

TitleStructures of dengue virus RNA replicase complexes.
Journal, issue, pagesMol Cell, Vol. 83, Issue 15, Page 2781-22791.e4, Year 2023
Publish dateAug 3, 2023
AuthorsTakuo Osawa / Mari Aoki / Haruhiko Ehara / Shun-Ichi Sekine /
PubMed AbstractDengue is a mosquito-borne viral infection caused by dengue virus (DENV), a member of the flaviviruses. The DENV genome is a 5'-capped positive-sense RNA with a unique 5'-stem-loop structure (SLA), ...Dengue is a mosquito-borne viral infection caused by dengue virus (DENV), a member of the flaviviruses. The DENV genome is a 5'-capped positive-sense RNA with a unique 5'-stem-loop structure (SLA), which is essential for RNA replication and 5' capping. The virus-encoded proteins NS5 and NS3 are responsible for viral genome replication, but the structural basis by which they cooperatively conduct the required tasks has remained unclear. Here, we report the cryoelectron microscopy (cryo-EM) structures of SLA-bound NS5 (PC), NS3-bound PC (PC-NS3), and an RNA-elongating NS5-NS3 complex (EC). While SLA bridges the NS5 methyltransferase and RNA-dependent RNA polymerase domains in PC, the NS3 helicase domain displaces it in elongation complex (EC). The SLA- and NS3-binding sites overlap with that of human STAT2. These structures illuminate the key steps in DENV genome replication, namely, SLA-dependent replication initiation, processive RNA elongation, and 5' capping of the nascent genomic RNA, thereby providing foundations to combat flaviviruses.
External linksMol Cell / PubMed:37478848
MethodsEM (single particle)
Resolution2.8 - 3.9 Å
Structure data

34400

8gzp

EMDB-34400, PDB-8gzp:
Cryo-EM structure of the NS5-SLA complex
Method: EM (single particle) / Resolution: 3.6 Å

34401

8gzq

EMDB-34401, PDB-8gzq:
Cryo-EM structure of the NS5-NS3-SLA complex
Method: EM (single particle) / Resolution: 3.9 Å

34402

8gzr

EMDB-34402, PDB-8gzr:
Cryo-EM structure of the the NS5-NS3 RNA-elongation complex
Method: EM (single particle) / Resolution: 2.8 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-GDP:
GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying molecule*YM / Guanosine diphosphate

ChemComp-MG:
Unknown entry

ChemComp-MN:
Unknown entry

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

ChemComp-CDP:
CYTIDINE-5'-DIPHOSPHATE / Cytidine diphosphate

Source
  • dengue virus
  • synthetic construct (others)
KeywordsVIRAL PROTEIN / viral genome replication

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