Structural basis for receptor recognition by Lujo virus

Nature Microbiology
Hadas Cohen-DvashiRon Diskin

Abstract

Lujo virus (LUJV) has emerged as a highly fatal human pathogen. Despite its membership among the Arenaviridae, LUJV does not classify with the known Old and New World groups of that viral family. Likewise, LUJV was recently found to use neuropilin-2 (NRP2) as a cellular receptor instead of the canonical receptors used by Old World and New World arenaviruses. The emergence of a deadly pathogen into human populations using an unprecedented entry route raises many questions regarding the mechanism of cell recognition. To provide the basis for combating LUJV in particular, and to increase our general understanding of the molecular changes that accompany an evolutionary switch to a new receptor for arenaviruses, we used X-ray crystallography to reveal how the GP1 receptor-binding domain of LUJV (LUJVGP1) recognizes NRP2. Structural data show that LUJVGP1 is more similar to Old World than to New World arenaviruses. Structural analysis supported by experimental validation further suggests that NRP2 recognition is metal-ion dependent and that the complete NRP2 binding site is formed in the context of the trimeric spike. Taken together, our data provide the mechanism for the cell attachment step of LUJV and present indispensable informa...Continue Reading

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Citations

Feb 18, 2020·Virus Evolution·Weng M NgThomas A Bowden
Jan 12, 2020·Nature Communications·Katherine LeonDemet Araç
Feb 16, 2020·Cell Host & Microbe·Hadas Cohen-DvashiRon Diskin
Feb 5, 2021·Journal of Virology·Yang LiuWei Wang
Nov 14, 2021·Proceedings of the National Academy of Sciences of the United States of America·Giuseppe BalistreriTambet Teesalu

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Methods Mentioned

BETA
X-ray
glycosylation
electrophoresis
fluorescence microscopy
size exclusion chromatography
PCR

Software Mentioned

AutoBuild
APBS
Coot
align
TM
CCP4
PyMol
Phaser
ImageJ
Phenix

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