ACE2/structural biology project: Difference between revisions
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Human ACE2 enzyme is composed of 805 amino acids. | Human ACE2 enzyme is composed of 805 amino acids. | ||
Extracelular region of the human ACE2 enzyme is composed of an N-terminal zinc metallopeptidase domain and a C-terminal collectrin-like domain | Extracelular region of the human ACE2 enzyme is composed of an N-terminal zinc metallopeptidase domain (PD) and a C-terminal collectrin-like domain (CLD) ends with a transmembrane helix and intracellular segment of 40 residues. | ||
Subdomains I(N-terminus) and II(C-terminus) of the metallopeptidase domain of ACE2 form two sides of a cleft and connected at the floor of the active site of the cleft. Helix 17 (residues 511-531) connects to the subdomains and forms part of the floor. | Subdomains I(N-terminus) and II(C-terminus) of the metallopeptidase domain of ACE2 form two sides of a cleft and connected at the floor of the active site of the cleft. Helix 17 (residues 511-531) connects to the subdomains and forms part of the floor. | ||
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A chloride ion is coordinated by Arg169, Trp477, and Lys481 in subdomain II. | A chloride ion is coordinated by Arg169, Trp477, and Lys481 in subdomain II. | ||
Srtuctural information is limited to the PD domain because of transmembrane helix which makes the determination of the structure troubling. | |||
== ACE2-B0AT1 complex == | == ACE2-B0AT1 complex == | ||
<Structure load='6M18' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /> | |||
In the context of the complex, dimerisation of the ACE2 is mediated by neck domain. That complex has both open and closed conformations observed<ref>PMID: 14754895</ref>. | In the context of the complex, dimerisation of the ACE2 is mediated by neck domain. That complex has both open and closed conformations observed<ref>PMID: 14754895</ref>. B0AT1 is coded by SLC6A19 gene. Mutations in that gene cause reduced activity of the B0AT1 protein, which leads to inability to absorb certain amino acids; and such condition is known as a Hurtnup disorder and may be inherited. | ||
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Also ACE2 plays role in regulation of the blood pressure<ref>PMID: 16788004</ref>. Highly expressed enzyme protects against hypertension. | Also ACE2 plays role in regulation of the blood pressure<ref>PMID: 16788004</ref>. Highly expressed enzyme protects against hypertension. | ||
== ACE2 as a microbal entry receptor == | |||
As a membrane protein, ACE2 serves as a functional receptor for coronaviruses, including SARS-CoV<ref>PMID:25720466</ref>, SARS-CoV-2(causes COVID19)<ref>DOI: 10.1126/science.abb2762</ref> and HCoV-NL63. S protein, also known as spike glycoprotein, mediates receptor recognition and fusion of the membrane<ref>PMID:24121034</ref>. During infection the cleavage of the S protein produces S1 and S2 subunits. S1 contains the receptor binding domain (RBD) and directly binds to the peptidase domain of ACE2 on the surface of cells. This spiking results in endocytosis and translocation of both virus and the enzyme, where S2 is responsible for the membrane fusion<ref>PMID:18227861</ref>. | |||
SARS-CoV RBD and SARS-CoV-2 RBD shares similarity<ref>DOI: 10.1126/science.abb2762</ref>; but various conformational deviations are found. Substitution from SARS-CoV_RBD to SARS-CoV-2-RBD of Val404→Lys417, Tyr442→Leu455, Leu443→Phe456, Phe460→Tyr473, and Asn479→Gln493 may change affinity for ACE2. | |||
<Structure load='2AJF' size='350' frame='true' align='right' caption='Insert caption here' scene='SARS-CoV-RBD' /> | |||
== References == | == References == | ||
<references/> | <references/> | ||
