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.