Background: Angiotensin-converting enzyme 2 (ACE2) is primarily involved in the maturation of angiotensin. It also represents the main receptor for the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) that caused a serious epidemic COVID-19. Available evidence indicates that at the cell membrane, ACE2 can form heteromeric complexes with other membrane proteins, including the amino acid transporter B0 AT1 and G protein-coupled receptors (GPCR).

Objective: It is well known that during the formation of quaternary structures, the configuration of every single monomer is re-shaped by its interaction pattern in the macromolecular complex. Therefore, it can be hypothesized that the affinity of ACE2 to the viral receptor-binding domain (RBD), when in a heteromeric complex, may depend on the associated partner.

Methods: By using established docking and molecular dynamics procedures, the reshaping of monomer was explored in silico to predict possible heterodimeric structures between ACE2 and GPCR, such as angiotensin and bradykinin receptors. The associated possible changes in the binding affinity between the viral RBD and ACE2 when in the heteromeric complexes were also estimated.

Results and Conclusion: The results provided support to the hypothesis that the heteromerization state of ACE2 may modulate its affinity to the viral RBD. If experimentally confirmed, ACE2 heteromerization may contribute to explain the observed differences in susceptibility to virus infection among individuals and to devise new therapeutic opportunities.

背景：血管紧张素转换酶 2 (ACE2) 主要参与血管紧张素的成熟。它还代表了导致严重流行的 COVID-19 的严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 的主要受体。现有证据表明，在细胞膜上，ACE2 可以与其他膜蛋白形成异聚复合物，包括氨基酸转运蛋白 B0 AT1 和 G 蛋白偶联受体 (GPCR)。

目的：众所周知，在四级结构的形成过程中，每个单体的构型都通过其在大分子复合物中的相互作用模式而重新塑造。因此，可以假设 ACE2 与病毒受体结合域 (RBD) 的亲和力在异聚复合物中时可能取决于相关的伴侣。

方法：通过使用已建立的对接和分子动力学程序，在计算机中探索单体的重塑以预测 ACE2 和 GPCR 之间可能的异二聚体结构，例如血管紧张素和缓激肽受体。还估计了在异聚复合物中病毒 RBD 和 ACE2 之间结合亲和力的相关可能变化。

结果和结论：结果支持ACE2的异聚化状态可能调节其对病毒RBD的亲和力的假设。如果实验证实，ACE2 异聚化可能有助于解释观察到的个体之间病毒感染易感性的差异，并设计新的治疗机会。