Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2

TLDR

Angiotensin‑converting enzyme 2 (ACE2) is the cellular receptor for SARS‑CoV and SARS‑CoV‑2, the virus responsible for the COVID‑19 pandemic. The study aims to present cryo‑electron microscopy structures of full‑length human ACE2 in complex with the neutral amino acid transporter B0AT1, with or without the SARS‑CoV‑2 spike receptor‑binding domain. Cryo‑EM was performed at 2.9 Å overall resolution, achieving 3.5 Å local resolution at the ACE2‑RBD interface, revealing the structural details of the ACE2‑B0AT1 complex. The ACE2‑B0AT1 complex assembles as a dimer of heterodimers, with ACE2’s collectrin‑like domain mediating homodimerization, and the RBD is recognized by ACE2’s extracellular peptidase domain mainly through polar residues, offering insights into coronavirus recognition and infection.

Abstract

Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome–coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious coronavirus disease 2019 (COVID-19) epidemic. Here, we present cryo–electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter 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, with a local resolution of 3.5 angstroms at the ACE2-RBD interface. 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. These findings provide important insights into the molecular basis for coronavirus recognition and infection.