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Structure paper

タイトル	Pre-initiation and elongation structures of full-length La Crosse virus polymerase reveal functionally important conformational changes.
ジャーナル・号・ページ	Nat Commun, Vol. 11, Issue 1, Page 3590, Year 2020
掲載日	2020年7月17日
著者	Benoît Arragain / Grégory Effantin / Piotr Gerlach / Juan Reguera / Guy Schoehn / Stephen Cusack / Hélène Malet /
PubMed 要旨	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 ...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.
リンク	Nat Commun / PubMed:32681014 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	3.02 - 3.961 Å
構造データ	11093 6z6g EMDB-11093: Cryo-EM map of La Crosse virus polymerase at pre-initiation stage PDB-6z6g: Cryo-EM structure of La Crosse virus polymerase at pre-initiation stage 手法: EM (単粒子) / 解像度: 3.06 Å EMDB-11095: Masked cryo-EM map of La Crosse virus polymerase cap-binding domain and mid domain 手法: EM (単粒子) / 解像度: 3.54 Å EMDB-11107: Masked cryo-EM map of La Crosse virus polymerase zinc-binding domain and mid domain 手法: EM (単粒子) / 解像度: 3.49 Å 11118 6z8k EMDB-11118, PDB-6z8k: La Crosse virus polymerase at elongation mimicking stage 手法: EM (単粒子) / 解像度: 3.02 Å PDB-6z6b: Structure of full-length La Crosse virus L protein (polymerase) 手法: X-RAY DIFFRACTION / 解像度: 3.961 Å
化合物	ChemComp-ZN: Unknown entry ChemComp-MG: Unknown entry / マグネシウムジカチオン
由来	bunyavirus la crosse (ウイルス) la crosse orthobunyavirus (ウイルス)
キーワード	VIRAL PROTEIN / RNA-dependent RNA polymerase / REPLICATION / viral polymerase / transcription / polymerase / La Crosse virus