B⁰AT1 Amino Acid Transporter Complexed With SARS-CoV-2 Receptor ACE2 Forms a Heterodimer Functional Unit: In Situ...

Area of Science:

• Gastroenterology and Virology
• Molecular and Cellular Biology

Background:

• Angiotensin-converting enzyme-2 (ACE2) is the SARS-CoV-2 receptor, highly expressed in the small intestine.
• ACE2 forms a quaternary complex with the B⁰AT1 amino acid transporter in enterocytes, potentially directing SARS-CoV-2 tropism to the GI tract.
• Gastrointestinal symptoms and viral shedding are common in COVID-19 patients.

Purpose of the Study:

• To investigate the functional unit of the ACE2:B⁰AT1 complex in enterocyte apical membranes.
• To determine the molecular weight of the functional unit using radiation inactivation.
• To understand the physiological role of ACE2-B⁰AT1 interaction in the gut for COVID-19 pathogenesis.

Main Methods:

• Purified enterocyte brush border membrane vesicles were used.
• High-energy electron radiation (16 MeV linear accelerator) was applied to vesicles.
• Radiation target theory was employed to determine the molecular weight of the functional unit.

Main Results:

• A functional unit of Na+-dependent neutral amino acid influx transport was identified.
• The target size molecular weight of this functional unit was determined to be 183.7 ± 16.8 kDa.
• This functional unit corresponds to the [ACE2:B⁰AT1] heterodimer within the larger quaternary complex.

Conclusions:

• The [ACE2:B⁰AT1] heterodimer functions as a discrete unit within the apical membrane.
• These findings support previous molecular modeling and gut-lung axis hypotheses regarding COVID-19.
• Understanding this interaction aids in developing strategies to mitigate COVID-19 gastrointestinal symptoms and long-term sequelae.