The study presents cryo-electron microscopy (cryo-EM) structures of full-length human angiotensin-converting enzyme 2 (ACE2) in complex with the neutral amino acid transporter B^aATI, both with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2. The overall resolution of the structures is 2.9 angstroms, with a local resolution of 3.5 angstroms at the ACE2-RBD interface. The ACE2-B^aATI complex forms a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain of ACE2 through polar residues. These findings provide insights into the molecular basis for coronavirus recognition and infection. The study also explores the interaction between ACE2 and B^aATI, suggesting that B^aATI may not be involved in dimerization, indicating that ACE2 can form homodimers even in the absence of B^aATI. The structure of the RBD-ACE2-B^aATI ternary complex reveals that two S protein trimers can bind simultaneously to an ACE2 homodimer, with the RBD accommodated by one PD domain. The study highlights the potential for structure-based design of binders to enhance affinity for ACE2 or the S protein, which could aid in developing decoy ligands or neutralizing antibodies to suppress viral infection.The study presents cryo-electron microscopy (cryo-EM) structures of full-length human angiotensin-converting enzyme 2 (ACE2) in complex with the neutral amino acid transporter B^aATI, both with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2. The overall resolution of the structures is 2.9 angstroms, with a local resolution of 3.5 angstroms at the ACE2-RBD interface. The ACE2-B^aATI complex forms a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain of ACE2 through polar residues. These findings provide insights into the molecular basis for coronavirus recognition and infection. The study also explores the interaction between ACE2 and B^aATI, suggesting that B^aATI may not be involved in dimerization, indicating that ACE2 can form homodimers even in the absence of B^aATI. The structure of the RBD-ACE2-B^aATI ternary complex reveals that two S protein trimers can bind simultaneously to an ACE2 homodimer, with the RBD accommodated by one PD domain. The study highlights the potential for structure-based design of binders to enhance affinity for ACE2 or the S protein, which could aid in developing decoy ligands or neutralizing antibodies to suppress viral infection.