The 3.8 Å resolution cryo-EM structure of Zika virus

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Science  22 Apr 2016:
Vol. 352, Issue 6284, pp. 467-470
DOI: 10.1126/science.aaf5316
  1. Fig. 1 The cryo-EM structure of ZIKV at 3.8 Å.

    (A) A representative cryo-EM image of frozen hydrated ZIKV, showing the distribution of virion phenotypes. Smooth, mature virus particles are shown enclosed in black boxes. A partially mature virus particle is identified by the yellow arrow. (B) A surface-shaded depth-cued representation of ZIKV, viewed down the icosahedral twofold axis. The asymmetric unit is identified by the black triangle. (C) A cross section of ZIKV showing the radial density distribution. Color coding in (B) and (C) is based on radii, as follows: blue, up to 130 Å; cyan, 131 to 150 Å; green, 151 to 190 Å; yellow, 191 to 230 Å; red, 231 Å and above. The region shown in blue fails to follow icosahedral symmetry, and therefore its density is uninterruptable, as is the case with other flaviviruses. (D) A plot of the Fourier shell correlation (FSC). Based on the 0.143 criterion for the comparison of two independent data sets, the resolution of the reconstruction is 3.8 Å. (E) The Cα backbone of the E and M proteins in the icosahedral ZIKV particle [same orientation as in (B)], showing the herringbone organization. The color code follows the standard designation of E protein domains I (red), II (yellow), and III (blue). (F) Representative cryo-EM electron densities of several amino acids of the E protein. Cyan indicates carbon atoms; dark blue, nitrogen atoms; red, oxygen atoms; and yellow, sulfur atoms. Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.

  2. Fig. 2 The structures of the ZIKV E and M proteins.

    (A) The E protein dimer is shown in ribbon form, viewed down the twofold axis. The color code follows the standard designation of E protein domains I (red), II (yellow) and III (blue). The underlying stem and transmembrane residues are shown (light pink). The fusion loop (green; fig. S1), the Asn154 glycan (ball-and-stick representation), and the variable loop surrounding the Asn154 glycan (cyan; residues 145 to 160) are shown. (B) Side view of the (E-M)2, showing the three E ectodomains, as well as the E stem-transmembrane domains (pink) and the M loop and stem-transmembrane domains (light blue; TM, transmembrane). The E and M transmembrane domains are found within the lipid bilayer (Fig. 1C). All residues of M (1 to 75) and all but three residues of E (1 to 501) were identified in the density. The Asn154 glycan from one monomer is labeled and can be seen projecting from the surface.

  3. Fig. 3 Comparison of the E protein of ZIKV with that of other flaviviruses.

    (A) The region of the E protein of ZIKV strain H/PF/2013 (highlighted yellow) and other ZIKV strains is aligned to that of representative mosquito-transmitted flaviviruses. About 40 residues of domain I, centered on the Asn154 glycosylation site, are compared. The conserved glycosylation site at Asn153–154 is highlighted in blue. Red arrows represent secondary structures of ZIKV (sheets). The glycosylation motif N-X-S/T is underlined. The sequences for the flaviviruses were obtained from the Virus Pathogen Database and Analysis Resource. Virus strains for which structural information was available were chosen where possible. GenBank genome accession codes for these viruses are as follows: ZIKV Uganda MR766a, AY632535; ZIKV Uganda MR766b, KU720415; ZIKV FPolynesia H/PF/2013, KJ776791; ZIKV Brazil SPH2015, KU321639; DENV1 SG/07K3640DK1/2008, GQ398255; DENV2 16681, NC001474; DENV3 SG/05K863DK1/2005, EU081190; DENV4 SG/06K2270DK1/2005, GQ398256; WNV Lin1 Kunjin MRM61C, D00246; WNV Lin2 NY99, DQ211652; JEV SA14, D90194; and YFV Asibi, AY640589. The sequence of the original isolate (ZIKV MR766) varies based on the information source; it remains unclear whether this strain was glycosylated at N154 at the time of isolation or whether the glycosylation was acquired during passage through mouse brain. The sequences were manually aligned based on the structures of ZIKV and DENV2. (B) Superposition of the Cα backbone of the ZIKV and DENV2 E and M proteins. The DENV2 proteins are shown in magenta, the ZIKV E protein is shown in cyan, and the ZIKV M protein is shown in yellow. (C) Electron density representing the glycan at Asn154 in ZIKV. (D) Superposition of the loop region surrounding the glycosylation site (ZIKV, 144 to 166; DENV2, 144 to 161) that flanks the Asn154 glycan in ZIKV (cyan) and the Asn153 glycan in DENV2 (magenta).

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