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@ARTICLE{Williams:602551,
author = {Williams, Harry and Thorkelsson, Sigurdur R and Vogel,
Dominik and Milewski, Morlin and Busch, Carola and Cusack,
Stephen and Gruenewald, Kay and Quemin, Emmanuelle and
Rosenthal, Maria},
title = {{S}tructural insights into viral genome replication by the
severe fever with thrombocytopenia syndrome virus {L}
protein},
journal = {Nucleic acids symposium series},
volume = {51},
number = {3},
issn = {0305-1048},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {PUBDB-2024-00649},
pages = {1424 - 1442},
year = {2023},
note = {part of this work was performed at the Cryo-EM multi-user
Facility at CSSB, headed by K.G. and sup-ported by the UHH
and DFG [INST 152/772-1, 774-1, 775-1, 776-1];},
abstract = {Severe fever with thrombocytopenia syndrome virus (SFTSV)
is a phenuivirus that has rapidly become endemic in several
East Asian countries. The large (L) protein of SFTSV, which
includes the RNA-dependent RNA polymerase (RdRp), is
responsible for catalysing viral genome replication and
transcription. Here, we present 5 cryo-electron microscopy
(cryo-EM) structures of the L protein in several states of
the genome replication process, from pre-initiation to
late-stage elongation, at a resolution of up to 2.6 Å. We
identify how the L protein binds the 5′ viral RNA in a
hook-like conformation and show how the distal 5′ and 3′
RNA ends form a duplex positioning the 3′ RNA terminus in
the RdRp active site ready for initiation. We also observe
the L protein stalled in the early and late stages of
elongation with the RdRp core accommodating a 10-bp
product-template duplex. This duplex ultimately splits with
the template binding to a designated 3′ secondary binding
site. The structural data and observations are complemented
by in vitro biochemical and cell-based mini-replicon assays.
Altogether, our data provide novel key insights into the
mechanism of viral genome replication by the SFTSV L protein
and will aid drug development against segmented
negative-strand RNA viruses.},
cin = {CSSB-LIV-KG},
ddc = {540},
cid = {I:(DE-H253)CSSB-LIV-KG-20220525},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
experiment = {EXP:(DE-MLZ)NOSPEC-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36651274},
UT = {WOS:000914839600001},
doi = {10.1093/nar/gkac1249},
url = {https://bib-pubdb1.desy.de/record/602551},
}