In the core, between the β4-7 strands, there is an additional extended insertion containing short β5-6 strands. The SARS-CoV-2 RBD has a twisted 5-stranded antiparallel beta-sheet with short connecting helices and loops. SARS-CoV-2’s RBD is located between residues 331-524 (or Thr333-Gly526 in a different study) of the S1 domain, which enables it to bind to ACE2 – and more strongly than SARS-CoV (according to some studies) – which may reflect the higher infectiousness of SARS-CoV-2 compared to SARS-CoV. The RBD of SARS-CoV-2’s S1 domain strongly binds to both human and bat ACE2. The S-domain of SARS-CoV-2 contains an RBD which enables it to bind to ACE2 and fuse into the membrane of epithelial cells. Similar to SARS-CoV, SARS-CoV-2 (the virus that causes COVID-19) binds to the ACE2 receptor to gain entry into respiratory and digestive epithelial cells. Image Credit: Kateryna Kon/ SARS-CoV-2 (COVID-19) Thus, whilst the core CoV domains remain very similar, their RBD sequence varies considerably, influencing differing receptor affinity. The MERS-CoV RBD (E367 and Y606) forms a complex with DDP-4’s extracellular domain (S39-P766). In MERS-CoV, a 1353-amino acid type I membrane glycoprotein assembles into trimers forming the ‘spikes’ which bind and fuse to the DPP4/CD26 receptor. ![]() Thus, the binding of the viral RBD on its S-domain is an essential step for membrane fusion and entry into target host cells, as it leads to the S2 domain to transit from a pre-fusion state to a stable post-fusion state anchoring it to the membrane.Ĭoncerning Middle East respiratory syndrome-related coronavirus (MERS-CoV), the virus that causes MERS, the key difference between MERS-Cov and SARS-CoV is the viral S-domain (S1). K390) lead to decreased affinity to ACE2. Specific mutations within RBD amino acid residues (e.g. One functional glycosylation site is sufficient to create an RBD fragment that can bind to ACE2. Within the S domain of SARS-CoV, there is a short domain (within the S1 subunit) containing just 2 glycosylation sites that secrete short fragments of RBD (by glycosylation) that fold and bind to the ACE2 receptor. Coronaviruses are dotted with such S domains all over their surface giving the appearance of a large distinctive ‘crown’ appearance and thus the name ‘corona’/crown, viruses.Įach S domain is around 20 nm surface projection that surrounds the periphery of the coronavirus and varies considerably between different coronaviruses. The entry of beta-coronaviruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV), the virus that causes SARS, requires the binding of its spike glycoprotein, ‘S’ domain, to the ACE2 receptor in the body. Typically, the S-domain is also the site of neutralizing antibodies. Specifically, these refer to a part of the ‘spike’ glycoprotein (S-domain) which is needed to interact with endogenous receptors to facilitate membrane fusion and delivery to the cytoplasm. Image Credit: Volodymyr Dvornyk/ What is a receptor-binding domain (RBD)?Ī receptor-binding domain (RBD) is a short immunogenic fragment from a virus that binds to a specific endogenous receptor sequence to gain entry into host cells. Model of structure of novel coronavirus spike receptor-binding domain (pink) complexed with its receptor ACE2 (blue). ![]() These are also the primary targets in the prevention and treatment of viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the virus that causes COVID-19. Osman Shabir, PhD Reviewed by Sophia CoveneyĪ receptor-binding domain (RBD) is a key part of a virus located on its ‘ spike’ domain that allows it to dock to body receptors to gain entry into cells and lead to infection.
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