Angiotensin-converting enzyme 2 (ACE2) was identified to be the functional receptor of SARS-CoV. A 193 amino acid fragment (amino acid 318-510) of SARS-CoV S protein was demonstrated to bind ACE2 more efficiently than the full S1 domain and was defined as the receptor-binding domain of SARS-Co-V. A loop sub-domain (asam amino 424-494) that directly contacts with ACE2 as further identified as the receptor-binding motif by crystal structure analysis. In the receptor-binding motif several amino acid residues were found to be critical for receptor binding and changes in these key residues resulted in different binding efficiency among different SARS-CoV isolates.