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TitleMolecular basis of differential receptor usage for naturally occurring CD55-binding and -nonbinding coxsackievirus B3 strains.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 119, Issue 4, Year 2022
Publish dateJan 25, 2022
AuthorsQingling Wang / Qian Yang / Congcong Liu / Guoqing Wang / Hao Song / Guijun Shang / Ruchao Peng / Xiao Qu / Sheng Liu / Yingzi Cui / Peiyi Wang / Wenbo Xu / Xin Zhao / Jianxun Qi / Mengsu Yang / George F Gao /
PubMed AbstractReceptor usage defines cell tropism and contributes to cell entry and infection. Coxsackievirus B (CVB) engages coxsackievirus and adenovirus receptor (CAR), and selectively utilizes the decay- ...Receptor usage defines cell tropism and contributes to cell entry and infection. Coxsackievirus B (CVB) engages coxsackievirus and adenovirus receptor (CAR), and selectively utilizes the decay-accelerating factor (DAF; CD55) to infect cells. However, the differential receptor usage mechanism for CVB remains elusive. This study identified VP3-234 residues (234Q/N/V/D/E) as critical population selection determinants during CVB3 virus evolution, contributing to diverse binding affinities to CD55. Cryoelectron microscopy (cryo-EM) structures of CD55-binding/nonbinding isolates and their complexes with CD55 or CAR were obtained under both neutral and acidic conditions, and the molecular mechanism of VP3-234 residues determining CD55 affinity/specificity for naturally occurring CVB3 strains was elucidated. Structural and biochemical studies in vitro revealed the dynamic entry process of CVB3 and the function of the uncoating receptor CAR with different pH preferences. This work provides detailed insight into the molecular mechanism of CVB infection and contributes to an in-depth understanding of enterovirus attachment receptor usage.
External linksProc Natl Acad Sci U S A / PubMed:35046043 / PubMed Central
MethodsEM (single particle)
Resolution2.2 - 3.68 Å
Structure data

EMDB-32179, PDB-7vxh:
Coxsackievirus B3 full particle at pH7.4 (VP3-234Q)
Method: EM (single particle) / Resolution: 2.95 Å

EMDB-32189, PDB-7vxz:
Coxsackievirus B3 at pH7.4 (VP3-234Q) incubation with coxsackievirus and adenovirus receptor for 20min
Method: EM (single particle) / Resolution: 3.19 Å

EMDB-32190, PDB-7vy0:
Coxsackievirus B3 full particle at pH7.4 (VP3-234N)
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-32194, PDB-7vy5:
Coxsackievirus B3 (VP3-234Q) incubation with CD55 at pH7.4
Method: EM (single particle) / Resolution: 3.15 Å

EMDB-32195, PDB-7vy6:
Coxsackievirus B3(VP3-234N) incubate with CD55 at pH7.4
Method: EM (single particle) / Resolution: 3.02 Å

EMDB-32207, PDB-7vyk:
Coxsackievirus B3 at pH7.4 (VP3-234Q) incubation with coxsackievirus and adenovirus receptor for 10min
Method: EM (single particle) / Resolution: 2.79 Å

EMDB-32208, PDB-7vyl:
Coxsackievirus B3 at pH5.5 (VP3-234Q) incubation with coxsackievirus and adenovirus receptor for 20min
Method: EM (single particle) / Resolution: 2.79 Å

EMDB-32209, PDB-7vym:
Coxsackievirus B3 at pH7.4 (VP3-234E) incubation with coxsackievirus and adenovirus receptor for 10min
Method: EM (single particle) / Resolution: 3.68 Å

EMDB-32250, PDB-7w14:
Coxsackievirus B3 at pH7.4 (VP3-234E) incubation with coxsackievirus and adenovirus receptor for 20min
Method: EM (single particle) / Resolution: 2.2 Å

EMDB-32251, PDB-7w17:
Coxsackievirus B3 full particle at pH7.4 (VP3-234E)
Method: EM (single particle) / Resolution: 2.5 Å

Chemicals

ChemComp-PLM:
PALMITIC ACID / Palmitic acid

Source
  • coxsackievirus b3
  • homo sapiens (human)
KeywordsVIRUS / CVB3 / VP3-234Q / full particle / coxsackievirus and adenovirus receptor / 20min / VP3-234N / CD55 / VP3-234E

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