User:Letícia Oliveira Rojas Cruz/Sandbox 1
From Proteopedia
(Difference between revisions)
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'''''Association with B0AT1''''' | '''''Association with B0AT1''''' | ||
- | The ACE2 protein can associate with the neutral amino acid transporter <scene name='10/1078774/B0at1_zoom2/1'>B0AT1</scene>, also known as SLC6A19. In this context, ACE2 first forms a <scene name='10/1083732/Dimer_ace2_final/2'>homodimer</scene>, where two ACE2 molecules interact side by side. Each ACE2 monomer then binds to one B0AT1 molecule. This results in a complex composed of '''{{Font color|darkviolet|two ACE2}}''' and '''{{Font color|salmon|two B0AT1}}''' molecules, which is commonly described as a <scene name='10/1083732/Ace2_and_b0at1/2'>dimer of heterodimers</scene>. This association is essential for the transport of neutral amino acids in intestinal cells and the anchoring of ACE2 in the cell membrane, keeping the catalytic site facing the extracellular environment. Although ACE2 dimerization occurs independently of B0AT1, the transporter plays a stabilizing role by interacting with the Collectrin-like Domain. | + | The ACE2 protein can associate with the neutral amino acid transporter <scene name='10/1078774/B0at1_zoom2/1'>B0AT1</scene>, also known as SLC6A19.<ref>PMID:32132184</ref> In this context, ACE2 first forms a <scene name='10/1083732/Dimer_ace2_final/2'>homodimer</scene>, where two ACE2 molecules interact side by side. Each ACE2 monomer then binds to one B0AT1 molecule. This results in a complex composed of '''{{Font color|darkviolet|two ACE2}}''' and '''{{Font color|salmon|two B0AT1}}''' molecules, which is commonly described as a <scene name='10/1083732/Ace2_and_b0at1/2'>dimer of heterodimers</scene>. This association is essential for the transport of neutral amino acids in intestinal cells and the anchoring of ACE2 in the cell membrane, keeping the catalytic site facing the extracellular environment. Although ACE2 dimerization occurs independently of B0AT1, the transporter plays a stabilizing role by interacting with the Collectrin-like Domain. <ref>PMID:32132184</ref> |
This ACE2-B0AT1 complex is anchored to the cell plasma membrane, keeping the ACE2 protein in an extracellular environment. The intermembrane region has apolar characteristics, since it must interact with the hydrophobic tails of the phospholipids. Analyzing the <scene name='10/1083732/Polaridade_2/2'>polarity</scene> of the complex, an '''{{Font color|gray|apolar region}}''' is observed in the B0AT1 region, showing that it is in this region where the complex is in contact with the plasma membrane. The '''{{Font color|orchid|polar regions}}''' (CLD and PD domains of ACE2) are located in the external region, without contact with the apolar region of the phospholipids. | This ACE2-B0AT1 complex is anchored to the cell plasma membrane, keeping the ACE2 protein in an extracellular environment. The intermembrane region has apolar characteristics, since it must interact with the hydrophobic tails of the phospholipids. Analyzing the <scene name='10/1083732/Polaridade_2/2'>polarity</scene> of the complex, an '''{{Font color|gray|apolar region}}''' is observed in the B0AT1 region, showing that it is in this region where the complex is in contact with the plasma membrane. The '''{{Font color|orchid|polar regions}}''' (CLD and PD domains of ACE2) are located in the external region, without contact with the apolar region of the phospholipids. | ||
=== ACE2 Dimerization === | === ACE2 Dimerization === | ||
- | ACE2 protein dimerization occurs independently of B0AT1 and involves both the Collectrin-like Domain (CLD) and regions from the Peptidase Domain (PD). | + | ACE2 protein dimerization occurs independently of B0AT1 and involves both the Collectrin-like Domain (CLD) and regions from the Peptidase Domain (PD).<ref>PMID:32132184</ref> |
'''''CLD Domain Interaction''''' | '''''CLD Domain Interaction''''' | ||
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In this region, there is an extensive network of polar interactions that stabilizes the ACE2 dimer. The most actively involved amino acid residues are between 636 and 658 and between 708 and 717, corresponding to the second and fourth helices of the CLD domain, respectively. | In this region, there is an extensive network of polar interactions that stabilizes the ACE2 dimer. The most actively involved amino acid residues are between 636 and 658 and between 708 and 717, corresponding to the second and fourth helices of the CLD domain, respectively. | ||
- | <scene name='10/1078774/Interacao_cation/2'>Polar cation-pi interactions</scene> occur between the amino acids '''{{Font color|slateblue|Arg652}}''' and '''{{Font color|turquoise|Tyr641}}''' of the opposite ACE2 molecule, and between '''{{Font color|slateblue|Arg710}}''' and '''{{Font color|turquoise|Tyr633}}'''. Additionally, <scene name='10/1078774/Lig_hidrogenio/1'>hydrogen bonds</scene> help stabilize the dimer interface: '''{{Font color|slateblue|Arg652}}''' forms a hydrogen bond with '''{{Font color|slateblue|Arg638}}''', which further interacts with '''{{Font color|slateblue|Gln653}}''', linked to '''{{Font color|turquoise|Asn636}}'''. Also, '''{{Font color|slateblue|Arg710}}''' forms a hydrogen bond with '''{{Font color|turquoise|Asn639}}''', and '''{{Font color|turquoise|Arg716}}''' connects with '''{{Font color|slateblue|Ser709}}''' and '''{{Font color|slateblue|Asp713}}'''. | + | <scene name='10/1078774/Interacao_cation/2'>Polar cation-pi interactions</scene> occur between the amino acids '''{{Font color|slateblue|Arg652}}''' and '''{{Font color|turquoise|Tyr641}}''' of the opposite ACE2 molecule, and between '''{{Font color|slateblue|Arg710}}''' and '''{{Font color|turquoise|Tyr633}}'''. Additionally, <scene name='10/1078774/Lig_hidrogenio/1'>hydrogen bonds</scene> help stabilize the dimer interface: '''{{Font color|slateblue|Arg652}}''' forms a hydrogen bond with '''{{Font color|slateblue|Arg638}}''', which further interacts with '''{{Font color|slateblue|Gln653}}''', linked to '''{{Font color|turquoise|Asn636}}'''. Also, '''{{Font color|slateblue|Arg710}}''' forms a hydrogen bond with '''{{Font color|turquoise|Asn639}}''', and '''{{Font color|turquoise|Arg716}}''' connects with '''{{Font color|slateblue|Ser709}}''' and '''{{Font color|slateblue|Asp713}}'''.<ref>PMID:32132184</ref> |
'''''Domain PD Interation''''' | '''''Domain PD Interation''''' | ||
- | In addition to the CLD, the Peptidase Domain (PD) also contributes to ACE2 dimerization. The amino acids '''{{Font color|slateblue|Cys133}}''', '''{{Font color|slateblue|Asn134}}''', '''{{Font color|slateblue|Asp136}}''', '''{{Font color|slateblue|Asn137}}''', '''{{Font color|slateblue|Gln139}}''', '''{{Font color|slateblue|Glu140}}''', and '''{{Font color|slateblue|Cys141}}''' form a <scene name='10/1083732/Loop_pd/2'>loop</scene> region within the PD. The two cysteines ('''{{Font color|slateblue|Cys133}}''' and '''{{Font color|slateblue|Cys141}}''') establish a disulfide bond, which stabilizes the loop conformation, supported by additional intraloop polar interactions. Furthermore, '''{{Font color|slateblue|Gln139}}''' forms a polar interaction with '''{{Font color|turquoise|Gln175}}''' from the other ACE2 monomer. | + | In addition to the CLD, the Peptidase Domain (PD) also contributes to ACE2 dimerization. The amino acids '''{{Font color|slateblue|Cys133}}''', '''{{Font color|slateblue|Asn134}}''', '''{{Font color|slateblue|Asp136}}''', '''{{Font color|slateblue|Asn137}}''', '''{{Font color|slateblue|Gln139}}''', '''{{Font color|slateblue|Glu140}}''', and '''{{Font color|slateblue|Cys141}}''' form a <scene name='10/1083732/Loop_pd/2'>loop</scene> region within the PD. The two cysteines ('''{{Font color|slateblue|Cys133}}''' and '''{{Font color|slateblue|Cys141}}''') establish a disulfide bond, which stabilizes the loop conformation, supported by additional intraloop polar interactions. Furthermore, '''{{Font color|slateblue|Gln139}}''' forms a polar interaction with '''{{Font color|turquoise|Gln175}}''' from the other ACE2 monomer.<ref>PMID:32132184</ref> |
=== SARS-CoV-2 Binding === | === SARS-CoV-2 Binding === | ||
- | '''{{Font color|crimson|ACE2}}''' <scene name='10/1083732/Sars_cov_2/2'>binds</scene> to the '''{{Font color|darkmagenta|Spike (S)}}''' glycoprotein of the SARS-CoV-2 virus, promoting its internalization into the cell. More specifically, binding occurs between the PD subunit of ACE2 and the receptor binding domain (RBD) of the S1 subunit of the S protein. Each PD binds to an RBD by polar bonds, with one ACE2 dimer accommodating two S protein trimers. | + | '''{{Font color|crimson|ACE2}}''' <scene name='10/1083732/Sars_cov_2/2'>binds</scene> to the '''{{Font color|darkmagenta|Spike (S)}}''' glycoprotein of the SARS-CoV-2 virus, promoting its internalization into the cell. More specifically, binding occurs between the PD subunit of ACE2 and the receptor binding domain (RBD) of the S1 subunit of the S protein. Each PD binds to an RBD by polar bonds, with one ACE2 dimer accommodating two S protein trimers.<ref>PMID:32132184</ref> |
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- | HOFFMANN, M. et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, v. 181, n. 2, p. 271–280, mar. 2020. | ||
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- | IWAI, M.; HORIUCHI, M. Devil and angel in the renin–angiotensin system: ACE–angiotensin II–AT1 receptor axis vs. ACE2–angiotensin-(1–7)–Mas receptor axis. Hypertension Research, v. 32, n. 7, p. 533–536, 22 maio 2009. | ||
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- | KEGG ENZYME. angiotensin-converting enzyme 2. Disponível em: <https://www.genome.jp/dbget-bin/www_bget?enzyme+3.4.17.23>. | ||
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- | LAMBERT, D. W.; HOOPER, N. M.; TURNER, A. J. Angiotensin-converting enzyme 2 and new insights into the renin–angiotensin system. Biochemical Pharmacology, v. 75, n. 4, p. 781–786, fev. 2008. | ||
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- | MILLET, J. K.; WHITTAKER, G. R. Physiological and molecular triggers for SARS-CoV membrane fusion and entry into host cells. Virology, v. 517, p. 3–8, abr. 2018. | ||
OUDIT, G. Y. et al. Angiotensin-converting enzyme 2—at the heart of the COVID-19 pandemic. Cell, v. 186, n. 5, p. 906–922, mar. 2023. | OUDIT, G. Y. et al. Angiotensin-converting enzyme 2—at the heart of the COVID-19 pandemic. Cell, v. 186, n. 5, p. 906–922, mar. 2023. | ||
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- | YAN, R. et al. Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2. Science, v. 367, n. 6485, 4 mar. 2020. |
Revision as of 18:12, 8 July 2025
Angiotensin-converting enzyme 2 (ACE2)
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