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Structure paper

TitleBypassing pan-enterovirus host factor PLA2G16.
Journal, issue, pagesNat Commun, Vol. 10, Issue 1, Page 3171, Year 2019
Publish dateJul 18, 2019
AuthorsJim Baggen / Yue Liu / Heyrhyoung Lyoo / Arno L W van Vliet / Maryam Wahedi / Jost W de Bruin / Richard W Roberts / Pieter Overduin / Adam Meijer / Michael G Rossmann / Hendrik Jan Thibaut / Frank J M van Kuppeveld /
PubMed AbstractEnteroviruses are a major cause of human disease. Adipose-specific phospholipase A2 (PLA2G16) was recently identified as a pan-enterovirus host factor and potential drug target. In this study, we ...Enteroviruses are a major cause of human disease. Adipose-specific phospholipase A2 (PLA2G16) was recently identified as a pan-enterovirus host factor and potential drug target. In this study, we identify a possible mechanism of PLA2G16 evasion by employing a dual glycan receptor-binding enterovirus D68 (EV-D68) strain. We previously showed that this strain does not strictly require the canonical EV-D68 receptor sialic acid. Here, we employ a haploid screen to identify sulfated glycosaminoglycans (sGAGs) as its second glycan receptor. Remarkably, engagement of sGAGs enables this virus to bypass PLA2G16. Using cryo-EM analysis, we reveal that, in contrast to sialic acid, sGAGs stimulate genome release from virions via structural changes that enlarge the putative openings for genome egress. Together, we describe an enterovirus that can bypass PLA2G16 and identify additional virion destabilization as a potential mechanism to circumvent PLA2G16.
External linksNat Commun / PubMed:31320648 / PubMed Central
MethodsEM (single particle)
Resolution2.43 - 3.56 Å
Structure data

7632

6cv1

EMDB-7632, PDB-6cv1:
CryoEM structure of human enterovirus D68 full particle (after incubation with heparin-derived hexasaccharide)
Method: EM (single particle) / Resolution: 2.76 Å

7633

6cv2

EMDB-7633, PDB-6cv2:
CryoEM structure of human enterovirus D68 full virion
Method: EM (single particle) / Resolution: 2.86 Å

7634

6cv3

EMDB-7634, PDB-6cv3:
CryoEM structure of human enterovirus D68 emptied particle
Method: EM (single particle) / Resolution: 3.56 Å

7635

6cv4

EMDB-7635, PDB-6cv4:
CryoEM structure of human enterovirus D68 emptied particle (after incubation with low molecular weight heparin)
Method: EM (single particle) / Resolution: 3.03 Å

7636

6cv5

EMDB-7636, PDB-6cv5:
CryoEM structure of human enterovirus D68 full particle (after incubation with low molecular weight heparin)
Method: EM (single particle) / Resolution: 2.79 Å

7638

6cvb

EMDB-7638, PDB-6cvb:
CryoEM structure of human enterovirus D68 in complex with 6'-sialyl-N-acetyllactosamine
Method: EM (single particle) / Resolution: 2.43 Å

Chemicals

ChemComp-HOH:
WATER

Source
  • enterovirus d68
KeywordsVIRUS / genome release / receptor

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