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Review
. 2006 May;80(9):4211-9.
doi: 10.1128/JVI.80.9.4211-4219.2006.

Animal origins of the severe acute respiratory syndrome coronavirus: insight from ACE2-S-protein interactions

Wenhui Li  1 , Swee-Kee Wong, Fang Li, Jens H Kuhn, I-Chueh Huang, Hyeryun Choe, Michael Farzan
Affiliations
Review

Animal origins of the severe acute respiratory syndrome coronavirus: insight from ACE2-S-protein interactions

Wenhui Li et al. J Virol. 2006 May.
No abstract available

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Figures

FIG. 1.
FIG. 1.
Receptor-binding domains of coronaviruses. A representation of the primary structures of SARS-CoV, mouse hepatitis virus (MHV), and two group 1 human coronaviruses (HCoV-NL63 and HCoV-229E) is shown. The receptor-binding domains of each coronavirus are shown in cyan. The RBD of HCoV-NL63 is preliminary. The SARS-CoV RBD is shown in greater detail, with glycosylation sites and the disulfide structure indicated. Red denotes the receptor-binding motif within the RBD. The RBM comprises a long loop in direct contact with ACE2.
FIG. 2.
FIG. 2.
Cocrystal of the SARS-CoV RBD bound to human ACE2. Cyan indicates a region of the RBD shared among group 2 coronaviruses, whereas red indicates the RBM, which is not homologous to that of other group 2 viruses. ACE2 is shown in white, with its cleft bearing the enzyme-active site facing forward and the membrane-associated C terminus at the bottom of the figure.
FIG. 3.
FIG. 3.
Bat SARS-CoV lacks an ACE2 RBM region. Alignment of a portion of the TOR2 SARS-CoV RBD with the equivalent region of bat SARS-CoV is shown. The RBM region is indicated in red. Residues that directly contact human ACE2 are shown in green, and residues 479 and 487 are indicated with arrows.
FIG. 4.
FIG. 4.
Summary of genetic and biochemical studies of SARS-CoV S-protein residues 479 and 487. (Top) The most frequently observed residues at positions 479 and 487 in sequences of viral genomes obtained during the 2002-2003 human SARS-CoV epidemic and the sporadic infections of 2003-2004 and from palm civets in a Guangdong marketplace. Note that a single isolated palm civet genome (from >20 sequences) encodes a threonine at 487, whereas all sequences from the 2002-2003 epidemic (>100 sequences) encode this threonine. (Bottom) The S-protein residues that confer the most-efficient binding to the ACE2 proteins of the indicated species. The entry for reservoir species is speculative, based on the observation that the ACE2 of at least one animal (mouse) prefers lysine at residue 479 and the additional observation that all but one sequence from the Guangdong marketplace animals encode a serine at residue 487.
FIG. 5.
FIG. 5.
The contact region between the SARS-CoV RBD and ACE2 is shown. Residues that convert rat ACE2 to an efficient receptor are shown in orange. ACE2 lysine 31, which prevents association with SZ3 S protein, is shown in magenta. Lysine 31 and lysine 353 are indicated by arrows, with the amino acids of palm civet, mouse, and rat ACE2 at these positions shown in parentheses. TOR2 S-protein residues asparagine 479 and threonine 487 are also indicated, with the GD03 and SZ3 amino acids at these positions shown in parentheses.
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References

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