Convergent evolution in the mechanisms of ACBD3 recruitment to picornavirus replication sites

PLoS Pathogens
Vladimira HorovaMartin Klima

Abstract

Enteroviruses, members of the family of picornaviruses, are the most common viral infectious agents in humans causing a broad spectrum of diseases ranging from mild respiratory illnesses to life-threatening infections. To efficiently replicate within the host cell, enteroviruses hijack several host factors, such as ACBD3. ACBD3 facilitates replication of various enterovirus species, however, structural determinants of ACBD3 recruitment to the viral replication sites are poorly understood. Here, we present a structural characterization of the interaction between ACBD3 and the non-structural 3A proteins of four representative enteroviruses (poliovirus, enterovirus A71, enterovirus D68, and rhinovirus B14). In addition, we describe the details of the 3A-3A interaction causing the assembly of the ACBD3-3A heterotetramers and the interaction between the ACBD3-3A complex and the lipid bilayer. Using structure-guided identification of the point mutations disrupting these interactions, we demonstrate their roles in the intracellular localization of these proteins, recruitment of downstream effectors of ACBD3, and facilitation of enterovirus replication. These structures uncovered a striking convergence in the mechanisms of how enterovi...Continue Reading

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Citations

Oct 5, 2019·Protein Science : a Publication of the Protein Society·Dominika ChalupskaEvzen Boura
Feb 29, 2020·Microbiology and Immunology·Yue LuLeiliang Zhang
Sep 26, 2020·Frontiers in Microbiology·Xinhong LiXiaoyue Chen
Apr 4, 2021·Viruses·Terry Jackson, Graham J Belsham
Jul 29, 2021·Open Biology·Aušra DomanskaSarah J Butcher

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Methods Mentioned

BETA
nucleotide exchange
NMR
microscale thermophoresis
co-immunoprecipitation assay
flow cytometry
transfection
co-immunoprecipitation
FRET
size exclusion chromatography
X-ray

Software Mentioned

CCP4 suite
NAMD
XDSAPP
Buccaneer
PDBViewer
XDS
Coot
Swiss
PPM
Phenix

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