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ACE2
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ACE2 e o Sars-Cov-2
Glicoproteína
(Proteína S, presente
no espinho do vírus é
ativada por proteases
A ACE2 transmembrana é o
receptor dos
Sars-Cov e Sars-Cov-2.
O Sars-Cov-2 se liga a
ACE2 pela proteína S
que interage com o
DP da enzima;
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ACE2 –B0AT1
▸ ACE2 também é necessária no Formando um complexo chamado
transporte de B0AT1 pela ACE2-B0AT1 Protoméro A
membrana. Protomero B (ACE2)
(ACE2)
Transportador de
aminoácidos neutros
Fig. 1. Overall structure of the
ACE2-B0AT1 complex. Protomero B Protomero A
(B0AT1) (B0AT1)
(B) Cryo-EM map of the ACE2-B0AT1 complex. The map is generated
by merging the focused refined maps shown in fig. S2. Protomer A
of ACE2 (cyan), protomer B of ACE2 (blue), protomer A of B0AT1
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(pink) and protomer B of B0AT1 (gray) are shown.
Fig. 1 Overall structure of the ACE2-B0AT1 complex
D Asp N Asn
E Glu Q Gln
Ligação de Próton-p F Phe R Arg
hidrogênio
H His S Ser
K Lys T Thr
(C) A weaker interface between PDs of ACE2.
(B) The primary dimeric interface is through the The only interaction is between Gln 139 and Gln175′,
neck domain in ACE2. Polar interactions are
L Leu V Val which are highlighted as spheres. The polar
represented by red dashed lines. residues that may contribute to the stabilization of
Y Tyr Gln139 are shown as sticks.
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Overall structure of the RBD-ACE2-B0AT1
complex
▸ RBDmFc purificado de SARS-CoV-2
foi analisado por Cryo-EM
juntamente com o complexo ACE2-
B0AT1;
▸ Apenas o estado fechado da ACE2
foi observado;
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Fig. 3. Overall structure of the RBD-ACE2-B0AT1 complex
(A) Cryo-EM map of the RBD-ACE2-B0AT1 complex. The overall reconstruction of the ternary complex at 2.9 Å is shown on the left. The inset shows the focused refined
map of RBD. The color scheme is the same as that in Fig. 1B, with the addition ofred and gold, which represent RBD protomers.(B) Overall structure of the RBD-ACE2-
B0AT1 complex. The color scheme is the same as that in Fig. 1C. The glycosylation moieties are shown as sticks.
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Interface between the RBD and ACE2
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Fig. 4 Interactions between SARS-CoV-2-RBD and ACE2 .
Forças de
Van der Waa
(A) The PD of ACE2 mainly engages the a1 helix in the recognition of the RBD. The a2 helix and the linker between b3 and b4 also contribute to the
interaction. Only oneRBD-ACE2 is shown. (B to D) Detailed analysis of the interface between SARS-CoV-2-RBD and ACE2. Polar interactions are
13 indicated by red dashed lines. NAG, Nacetylglucosamine.
Comparing the SARS-CoV-2 and SARS-
CoV interfaces with ACE2
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Fig. 5. Interface comparison between SARS-CoV-2-RBD and SARS-CoV-RBD with ACE2.
(A) Structural alignment
for the SARS-CoV-2-
RBD and SARS-
CoVRBD. The structure
of the ACE2-PD and the Mudança mais
SARS-CoV-RBD significativa
complex (PDB2AJF) is
superimposed on our
cryo-EM structure of the
ternary complex relative
to the RBDs. The regions
enclosed by the purple,
blue, and red dashed lines
are illustrated in detail in
(B) to (D), respectively.
SARS-CoV-2-RBD and
the PD in our cryo-EM
structure are colored
orange and cyan, Aumento nas
respectively; SARS-CoV-
RBD and its complexed forças Van der
PD are colored green and Waals;
gold, respectively. (B to
D) Variation of the
interface residues
between SARS-CoV-2-
RBD (labeled in brown)
and SARS-CoV-RBD
(labeled in green).
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Discussão
▸ Embora o ACE2 seja um acompanhante para o B0AT1, nosso foco está no ACE2
neste estudo;
▸ B0AT1 não está envolvido na dimerização, sugerindo que o ACE2 pode ser um
homodímero;
▸ A estrutura trimérica da proteína S do SARSCoV-2 foi recentemente relatada, com
um RBD em uma conformação ascendente e dois em conformações descendentes;
▸ A DP entra em conflito com o restante da proteína S;
▸ Não há conflito quando o complexo é sobreposto ao RDB na conformação
ascendente.
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Discussão
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Referencias Bibliográficas
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