1050 4 MARCH 2022¥VOL 375 ISSUE 6584 science.orgSCIENCE
Fig. 2. Structure of the ACE2-bound
Omicron spike trimer complex and
epitopes of current antibodies.
(A) Cryo-EM density of the ACE2-
Omicron spike trimer complex.
(B) Overall structure of the ACE2-
Omicron spike trimer complex
and locations of the Omicron
mutations. Epitope hotspots are
highlighted in red circles, with the
number of antibodies indicated
next to the epitopes. (C) Histogram
of epitope corresponding with
residue numbers. Each epitope was
counted if more than three heavy
atoms of the residue were closer
than 5 Å with the antibody. The
PDB IDs and corresponding epitopes
are summarized in table S2 in the
supplementary materials.
Residue number(^20) NTD (^286319) RBD 541
N-term C-term
1
145-159 & 246-257
Hotspot I
335-422
Hotspot II
437-509
Hotspot III
Epitope number
H655Y
N856K N764K
Q954H
N969K
L981F
D614G
D796Y
43 antibodies
210 antibodies: AZD1061,
REGN10933, REGN10987
110 antibodies:
LY-CoV555
T547K
E484A
S477N
T478K
G446S
Q493R
K417N
N440K
501Y
Q498R
S373P Y505H
G496S
S371L
G339D
AB
C
S375F
RBD
NTD
G142D
L212I
Ins214EPE
T95I
Δ211
Δ143-145
Δ69-70
NTD
ACE2
RBD-1 up
RBD-2 down
N
Fig. 3. Structural analysis of Omicron RBD
and ACE2.(A) Cryo-EM density of the Omicron
RBD-RBD-ACE2 interface. ACE2 is colored in orange.
The ACE2-bound RBD (also called the up RBD) is
shown in purple. The down RBD, which directly
binds to up RBD, is shown in green. Left panel is
a magnified view of the RBD-RBD interaction.
Middle panel is an overall cryo-EM density of the
down RBD-RBD–ACE2 region. Right panel is
the ACE2-RBD–binding interface. Residues are
shown in sticks, with the correspondent cryo-EM
density represented in mesh. (B) Overall structural
model of Omicron RBD-ACE2–bound region.
(C) Magnified view of Omicron RBD-ACE2 with
hydrogen bond interactions. (D) Detailed hydrogen
bond interactions in WT RBD-ACE2 interfaces with
the same view as in (B). WT RBD is shown in
blue, Omicron RBD in purple, and ACE2 in orange.
Hydrogen bond or salt bridge interactions are
shown as dotted lines.
ACE2
Omicron
RBD
D38H34
Q42
Y501 S19
R498
R493
Y473
F456
T385 D30
A475 F486
Y369
K386
F374 L368
ACE2
Up RBD
ACE2
RBD
Y505
G496
Q498
N501
D38
Y41 Q42
D355
E37
S477
E484
D30
K31 Y83
F28
H34
K417
E35
2 Hydrogen bonds
WT RBD 2 Salt bridges
WT RBD
D355
Y41 Q42
R498
Y501
H505 S496
K353
D38
Y83
E35 F28
K31
N417R493
H34
F490
A484
N477
S19
2 Salt bridges
4 Hydrogen bonds
ACE2
Omicron RBD Omicron RBD
B ACE2
A
D
C
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