Pre-initiation and elongation structures of full-length La Crosse virus polymerase reveal functionally important conformational changes - Archive ouverte HAL Access content directly
Journal Articles Nature Communications Year : 2020

Pre-initiation and elongation structures of full-length La Crosse virus polymerase reveal functionally important conformational changes

Abstract

Bunyavirales is an order of segmented negative-strand RNA viruses comprising several life-threatening pathogens against which no effective treatment is currently available. Replication and transcription of the RNA genome constitute essential processes performed by the virally encoded multi-domain RNA-dependent RNA polymerase. Here, we describe the complete high-resolution cryo-EM structure of La Crosse virus polymerase. It reveals the presence of key protruding C-terminal domains, notably the cap-binding domain, which undergoes large movements related to its role in transcription initiation, and a zinc-binding domain that displays a fold not previously observed. We capture the polymerase structure at pre-initiation and elongation states, uncovering the coordinated movement of the priming loop, mid-thumb ring linker and lid domain required for the establishment of a ten-base-pair template-product RNA duplex before strand separation into respective exit tunnels. These structural details and the observed dynamics of key functional elements will be instrumental for structure-based development of polymerase inhibitors.

Dates and versions

hal-02907948 , version 1 (28-07-2020)

Identifiers

Cite

Benoît Arragain, Grégory Effantin, Piotr Gerlach, Juan Reguera, Guy Schoehn, et al.. Pre-initiation and elongation structures of full-length La Crosse virus polymerase reveal functionally important conformational changes. Nature Communications, 2020, 11 (1), pp.3590. ⟨10.1038/s41467-020-17349-4⟩. ⟨hal-02907948⟩
94 View
0 Download

Altmetric

Share

Gmail Facebook X LinkedIn More