6Y6K

Cryo-EM structure of a Phenuiviridae L protein

Summary for 6Y6K

• Entry DOI: 10.2210/pdb6y6k/pdb
• Related: 6XYA
• EMDB information: 10706
• Descriptor: RNA-dependent RNA polymerase, MAGNESIUM ION (2 entities in total)
• Functional Keywords: bunyavirus, phenuiviridae, l protein, viral polymerase, cap-snatching, viral protein
• Biological source: SFTS virus AH12
• Total number of polymer chains: 1
• Total formula weight: 235766.84

Authors

Vogel, D.,Thorkelsson, S.R.,Quemin, E.,Meier, K.,Kouba, T.,Gogrefe, N.,Busch, C.,Reindl, S.,Guenther, S.,Cusack, S.,Gruenewald, K.,Rosenthal, M. (deposition date: 2020-02-26, release date: 2020-04-08, Last modification date: 2024-05-22)

Primary citation

Vogel, D.,Thorkelsson, S.R.,Quemin, E.R.J.,Meier, K.,Kouba, T.,Gogrefe, N.,Busch, C.,Reindl, S.,Gunther, S.,Cusack, S.,Grunewald, K.,Rosenthal, M.
Structural and functional characterization of the severe fever with thrombocytopenia syndrome virus L protein.
Nucleic Acids Res., 48:5749-5765, 2020

PubMed Abstract: The Bunyavirales order contains several emerging viruses with high epidemic potential, including Severe fever with thrombocytopenia syndrome virus (SFTSV). The lack of medical countermeasures, such as vaccines and antivirals, is a limiting factor for the containment of any virus outbreak. To develop such antivirals a profound understanding of the viral replication process is essential. The L protein of bunyaviruses is a multi-functional and multi-domain protein performing both virus transcription and genome replication and, therefore, is an ideal drug target. We established expression and purification procedures for the full-length L protein of SFTSV. By combining single-particle electron cryo-microscopy and X-ray crystallography, we obtained 3D models covering ∼70% of the SFTSV L protein in the apo-conformation including the polymerase core region, the endonuclease and the cap-binding domain. We compared this first L structure of the Phenuiviridae family to the structures of La Crosse peribunyavirus L protein and influenza orthomyxovirus polymerase. Together with a comprehensive biochemical characterization of the distinct functions of SFTSV L protein, this work provides a solid framework for future structural and functional studies of L protein-RNA interactions and the development of antiviral strategies against this group of emerging human pathogens.

PubMed: 32313945
DOI: 10.1093/nar/gkaa253

Experimental method

ELECTRON MICROSCOPY (3.78 Å)