Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Cryo-EM structures of Lassa and Machupo virus polymerases complexed with cognate regulatory Z proteins identify targets for antivirals.
Journal, issue, pages	Nat Microbiol, Vol. 6, Issue 7, Page 921-931, Year 2021
Publish date	Jun 14, 2021
Authors	Xin Xu / Ruchao Peng / Qi Peng / Min Wang / Ying Xu / Sheng Liu / Xiaolin Tian / Haiteng Deng / Yimin Tong / Xiaoyou Hu / Jin Zhong / Peiyi Wang / Jianxun Qi / George F Gao / Yi Shi /
PubMed Abstract	Zoonotic arenaviruses can lead to life-threating diseases in humans. These viruses encode a large (L) polymerase that transcribes and replicates the viral genome. At the late stage of replication, ...Zoonotic arenaviruses can lead to life-threating diseases in humans. These viruses encode a large (L) polymerase that transcribes and replicates the viral genome. At the late stage of replication, the multifunctional Z protein interacts with the L polymerase to shut down RNA synthesis and initiate virion assembly. However, the mechanism by which the Z protein regulates the activity of L polymerase is unclear. Here, we used cryo-electron microscopy to resolve the structures of both Lassa and Machupo virus L polymerases in complex with their cognate Z proteins, and viral RNA, to 3.1-3.9 Å resolutions. These structures reveal that Z protein binding induces conformational changes in two catalytic motifs of the L polymerase, and restrains their conformational dynamics to inhibit RNA synthesis, which is supported by hydrogen-deuterium exchange mass spectrometry analysis. Importantly, we show, by in vitro polymerase reactions, that Z proteins of Lassa and Machupo viruses can cross-inhibit their L polymerases, albeit with decreased inhibition efficiencies. This cross-reactivity results from a highly conserved determinant motif at the contacting interface, but is affected by other variable auxiliary motifs due to the divergent evolution of Old World and New World arenaviruses. These findings could provide promising targets for developing broad-spectrum antiviral drugs.
External links	Nat Microbiol / PubMed:34127846
Methods	EM (single particle)
Resolution	3.1 - 4.1 Å
Structure data	30387 7ckl EMDB-30387, PDB-7ckl: Structure of Lassa virus polymerase bound to Z matrix protein Method: EM (single particle) / Resolution: 3.88 Å 30388 7ckm EMDB-30388, PDB-7ckm: Structure of Machupo virus polymerase bound to Z matrix protein (monomeric complex) Method: EM (single particle) / Resolution: 3.37 Å 31177 7el9 EMDB-31177, PDB-7el9: Structure of Machupo virus L polymerase in complex with Z protein and 3'-vRNA (dimeric complex) Method: EM (single particle) / Resolution: 3.2 Å 31178 7ela EMDB-31178, PDB-7ela: Structure of Lassa virus polymerase in complex with 3'-vRNA and Z mutant (F36A) Method: EM (single particle) / Resolution: 3.4 Å 31179 7elb EMDB-31179, PDB-7elb: Structure of Machupo virus L polymerase in complex with Z protein (dimeric form) Method: EM (single particle) / Resolution: 4.1 Å 31180 7elc EMDB-31180: Monomeric complex of MACV L bound to Z and 3'-vRNA PDB-7elc: Structure of monomeric complex of MACV L bound to Z and 3'-vRNA Method: EM (single particle) / Resolution: 3.1 Å
Chemicals	ChemComp-MN: Unknown entry ChemComp-ZN: Unknown entry
Source	lassa mammarenavirus machupo mammarenavirus machupo virus
Keywords	VIRAL PROTEIN / Lassa virus / Polymerase / Z protein / replication regulation / Machupo virus / VIRAL PROTEIN/RNA / RNA virus / replication / transcription / matrix protein / VIRAL PROTEIN-RNA complex