2.A.22.6.3
B(O)AT1 or BOAT (SLC6A19; Hartnup's disease protein) is a kidney and intestinal apical membrane epithelial transporter for Na⁺-dependent, Cl^--independent reabsorption of neutral amino acids. Many neutral L-amino acids bind with ~0.5 mM affinities; Leu is the preferred substrate, but all large, neutral, non-aromatic, L-amino acids bind to this transporter. Uptake of leucine is sodium-dependent. In contrast to other members of the neurotransmitter transporter family, this one does not appear to be chloride-dependent.  Activity is enhanced by collectrin (Tmem27), a collecting duct transmembrane (1 TMS) glycoprotein (Q9HBJ8) (Danilczyk et al., 2006). The mouse orthologue is (Q9D687) (Broer et al., 2004; 2008) which is deficient due to mutation(s) in its structural gene, and it forms a complex with collectrin and the brush border carboxypeptidase angiotensin-converting enzyme 2 (ACE2; Q9BYF1). Mutations in Hartnup disorder protein, such as B₀AT1(R240Q), decrease complex formation (Kraut and Sachs 2005) and lead to neutral aminoaciduria and in some cases pellagra-like symptoms (Kowalczuk et al., 2008; Singer et al. 2012).  Collectrin is expressed at high levels in the simple embryonic kidney (the pronephros) of amphibians such as Xenopus  (McCoy et al. 2008). ACE2 plays an important role in amino acid transport by acting as a binding partner of SLC6A19 in  the intestine, regulating its trafficking, expression on the cell surface and catalytic activity (Kowalczuk et al. 2008, Camargo et al. 2009). ACE2 is also the cellular receptor for SARS-CoV and SARS-CoV-2 ( causitive agent of COVID-19). Yan et al. 2020 presented cryoEM structures of full-length human ACE2 in the presence of B⁰AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 angstroms. The ACE2-B⁰AT1 complex is assembled as a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain of ACE2 mainly through polar residues (Yan et al. 2020).