User:Letícia Oliveira Rojas Cruz/Sandbox 1

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The '''<scene name='10/1083732/Peptidase_domain/2'>Peptidase Domain</scene>''' is responsible for the enzymatic activity of ACE2. This domain can be divided in two subdomains: <scene name='10/1083732/Subdominio_1_nterm/2'>Subdomain I</scene> (residues 19–400) and <scene name='10/1083732/Subdominio_2_cterm/2'>Subdomain II</scene> (residues 401–615). Together, they form a substrate-binding cleft, where is located the '''<scene name='10/1083732/Sitio_zinco_com_residuos/1'>catalytic site</scene>''', denominated '''HEXXH+E zinc-binding motif'''. Within this site, a '''{{Font color|lime|zinc-ion}}''' is associated with the residues '''His374''', '''His378''', and '''Glu402''', which are going to perform a nucleophilic attack on the peptide bond of the substrate, leading to its cleavage. '''<scene name='10/1083732/Peptidase_domain_hydrofobic/2'>Hydrophobic portions</scene>''' within each subdomain, composed mainly of nonpolar residues provide tertiary structural stability, maintaining the correct spatial arrangement of catalytic residues. In the animation, we can observe a concentration of the '''{{Font color|gray|hydrophobic residues}}''' towards the center of the molecule, while the '''{{Font color|orchid|polar}}''' ones are towards the outside part of the molecule.
The '''<scene name='10/1083732/Peptidase_domain/2'>Peptidase Domain</scene>''' is responsible for the enzymatic activity of ACE2. This domain can be divided in two subdomains: <scene name='10/1083732/Subdominio_1_nterm/2'>Subdomain I</scene> (residues 19–400) and <scene name='10/1083732/Subdominio_2_cterm/2'>Subdomain II</scene> (residues 401–615). Together, they form a substrate-binding cleft, where is located the '''<scene name='10/1083732/Sitio_zinco_com_residuos/1'>catalytic site</scene>''', denominated '''HEXXH+E zinc-binding motif'''. Within this site, a '''{{Font color|lime|zinc-ion}}''' is associated with the residues '''His374''', '''His378''', and '''Glu402''', which are going to perform a nucleophilic attack on the peptide bond of the substrate, leading to its cleavage. '''<scene name='10/1083732/Peptidase_domain_hydrofobic/2'>Hydrophobic portions</scene>''' within each subdomain, composed mainly of nonpolar residues provide tertiary structural stability, maintaining the correct spatial arrangement of catalytic residues. In the animation, we can observe a concentration of the '''{{Font color|gray|hydrophobic residues}}''' towards the center of the molecule, while the '''{{Font color|orchid|polar}}''' ones are towards the outside part of the molecule.
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The following domain is the '''<scene name='10/1083732/Collectrin-like_domain/3'>Collectrin-like Domain</scene>''', formed by '''{{Font color|gold|4 beta sheets}}''' and '''{{Font color|deeppink|3 alpha-helices}}''' that make a hydrophobic core, structure that is important for stabilizing ACE2 dimers, which will be represented later on this page.
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The following domain is the '''<scene name='10/1083732/Collectrin-like_domain/3'>Collectrin-like Domain</scene>''' (CLD), formed by '''{{Font color|gold|4 beta sheets}}''' and '''{{Font color|deeppink|3 alpha-helices}}''' that make a hydrophobic core, structure that is important for stabilizing ACE2 dimers, which will be represented later on this page.
The <scene name='10/1083732/Transmembrane_domain/1'>Transmembrane Domain</scene> is composed of a '''{{Font color|red|single alpha helix}}''', made of a majority of <scene name='10/1083732/Transmembrane_domain_hydrop/1'>hydrophobic residues</scene> (in '''{{Font color|gray|gray}}'''). This characteristic allows ACE2 to be anchored in the plasma membrane, due to its hydrophobic nature.
The <scene name='10/1083732/Transmembrane_domain/1'>Transmembrane Domain</scene> is composed of a '''{{Font color|red|single alpha helix}}''', made of a majority of <scene name='10/1083732/Transmembrane_domain_hydrop/1'>hydrophobic residues</scene> (in '''{{Font color|gray|gray}}'''). This characteristic allows ACE2 to be anchored in the plasma membrane, due to its hydrophobic nature.
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In this disease, ACE2 acts as a viral receptor, to which the Spike (S) viral protein binds, promoting the entry of the virus into the host cell. The specific region of the S protein responsible for binding to the ACE2 receptor is called '''receptor-binding domain (RBD)''', and is located in the S1 subunit of the Spike protein.
In this disease, ACE2 acts as a viral receptor, to which the Spike (S) viral protein binds, promoting the entry of the virus into the host cell. The specific region of the S protein responsible for binding to the ACE2 receptor is called '''receptor-binding domain (RBD)''', and is located in the S1 subunit of the Spike protein.
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== Disease ==
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=== Structure highlights ===
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==== ACE2-B0AT1 Complex ====
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===== Association with B0AT1 =====
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The ACE2 protein can associate with the neutral amino acid transporter B0AT1, also known as SLC6A19. In this context, ACE2 first forms a homodimer, where two ACE2 molecules interact side by side. Each ACE2 monomer then binds to one B0AT1 molecule. This results in a complex composed of two ACE2 and two B0AT1 molecules, which is commonly described as a dimer of heterodimers. 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
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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 polarity of the complex, an apolar (in gray) 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 polar regions (CLD and PD domains of ACE2) are located in the external region, without contact with the apolar region of the phospholipids.
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==== ACE2 Dimerization ====
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ACE2 protein dimerization occurs independently of B0AT1 and presents interaction of the CLD domain, with contribution from the PD domain.
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''''' 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.
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Polar cation-π interactions occur between the amino acids Arg652 and Tyr641 of the other ACE2 molecule, and between Arg710 and Tyr633. Hydrogen bonds are also present: Arg652 with Asn638, this with Gln653 and this with Asn636; Arg710 with Glu639 and, finally, Arg716 with Ser709 and Asp713.
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'''''Domain PD Interation'''''
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This structure is made up of a loop in one of the ACE2 chains, in which the amino acids Cys133, Asn134, Asp136, Asn137, Gln139, Glu140 and Cys141 are present. The two cysteines form a disulfide bond that stabilizes the loop along with intraloop polar interactions. Gln139 binds to Gln175 of the other ACE2 chain by polar interaction.
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== Relevance ==
 
== Structural highlights ==
== Structural highlights ==

Revision as of 18:53, 22 June 2025

Introduction

Caption for this structure

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References

Proteopedia Page Contributors and Editors (what is this?)

Letícia Oliveira Rojas Cruz

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