Transmissibility of SARS-CoV-2 initially relies on its trimeric Spike-RBDs to tether the ACE-2 on host cells, and enhanced self-association of ACE-2 engaged with Spike facilitates the viral infection. Two primary packing modes of Spike-ACE2 heteroproteins exist potentially due to discrepant amounts of RBDs loading on ACE-2, but the resultant self-association difference is inherently unclear. We used extensive coarse-grained dynamic simulations to characterize the self-association efficiency, the conformation relevance, and the molecular mechanism of ACE-2 with different RBD amounts. It was revealed that the ACE-2 hanging two/full RBDs (Mode-A) rapidly dimerized into the heteroprotein complex in a compact "linear" conformation, while the bare ACE-2 showed weakened self-association and a protein complex. The RBD-tethered ectodomains of ACE-2 presented a more upright conformation relative to the membrane, and the intermolecular ectodomains were predominantly packed by the neck domains, which was obligated to the rapid protein self-association in a compact pattern. Noted is the fact that the ACE-2 tethered by a single RBD (Mode-B) retained considerable self-association efficiency and clustering capability, which unravels the interrelation of ACE-2 colocalization and protein cross-linkage. The molecular perspectives in this study expound the self-association potency of ACE-2 with different RBD amounts and the viral activity implications, which can greatly enhance our comprehension of SARS-CoV-2 infection details.