B0AT1 (SLC6A19) and SIT1 (SLC6A20) are special members of the SLC6 family that rely on the ancillary protein Angiotensin-converting enzyme 2 (ACE2) or Collectrin for their membrane trafficking. ACE2 functions as a peptidase that regulates the maturation of angiotensin (Ang) and serves as the critical host receptor for SARS-CoV-2, while Collectrin is a homolog of ACE2 with a similar tissue distribution, including the liver and kidneys. B0AT1 is responsible for the uptake of neutral amino acids such as glutamine (Gln), leucine (Leu), and methionine (Met). Mutations in the SLC6A19 gene have been associated with a rare genetic disorder called Hartnup disease, characterized by impaired absorption of neutral amino acids in the small intestines and kidneys, leading to skin rashes, neurological symptoms, and even psychiatric disorders. On the other hand, SIT1 primarily facilitates the transport of imino acids such as proline (Pro) and pipecolate. Mutations in the SLC6A20 gene have been linked to a rare genetic disorder known as iminoglycinuria. This disorder is characterized by impaired renal reabsorption of imino acids, resulting in excessive excretion of these imino acids into the urine. Furthermore, the expression levels of SLC6A20 are closely associated with the risk and severity of COVID-19 infection. Overexpression of SIT1 has been shown to notably decrease the receptor binding domain (RBD) of SARS-CoV-2 binding to human cells, possibly by trapping ACE2 in the cytosol. This suggests a close relationship among ACE2, SIT1, and SARS-CoV-2. Here you can see a recent cryoEM structure of the human ACE2-B0AT1 complex bound with glutamine (PDB code: 8I92)

#molecularart ... #immolecular ... #glutamine ... #transporter ... #complex ... #ace2 ... #boat1 ... #cryoem

Structure rendered with @proteinimaging and depicted with @corelphotopaint