6CVB

CryoEM structure of human enterovirus D68 in complex with 6'-sialyl-N-acetyllactosamine

Summary for 6CVB

• Entry DOI: 10.2210/pdb6cvb/pdb
• EMDB information: 7632 7633 7634 7635 7636 7638
• Related PRD ID: PRD_900046
• Descriptor: viral protein 1, viral protein 3, viral protein 2, ... (6 entities in total)
• Functional Keywords: virus, genome release, receptor
• Biological source: Enterovirus D68; More
• Total number of polymer chains: 4
• Total formula weight: 95735.12

Authors

Liu, Y.,Rossmann, M.G. (deposition date: 2018-03-27, release date: 2019-07-24, Last modification date: 2024-03-13)

Primary citation

Baggen, J.,Liu, Y.,Lyoo, H.,van Vliet, A.L.W.,Wahedi, M.,de Bruin, J.W.,Roberts, R.W.,Overduin, P.,Meijer, A.,Rossmann, M.G.,Thibaut, H.J.,van Kuppeveld, F.J.M.
Bypassing pan-enterovirus host factor PLA2G16.
Nat Commun, 10:3171-3171, 2019

PubMed Abstract: 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.

PubMed: 31320648
DOI: 10.1038/s41467-019-11256-z

Experimental method

ELECTRON MICROSCOPY (2.43 Å)