Coronavirus Spike-RBD Variants Differentially Bind to the Human ACE2 Receptor
Feinstein, P.
Show abstract
The SARS-CoV-2 betacoronavirus infects people through binding the human Angiotensin Receptor 2 (ACE2), followed by import into a cell utilizing the Transmembrane Protease, Serine 2 (TMPRSS2) and Furin cofactors. Analysis of the SARS-CoV-2 extracellular spike protein has suggested critical amino acids necessary for binding within a 197-residue portion, the receptor binding domain (RBD). A cell-based assay between a membrane tethered RBD-GFP fusion protein and the membrane bound ACE2-Cherry fusion protein allowed for mutational intersection of both RBD and ACE2 proteins. Data shows Omicron BA.1 and BA.2 variants have altered dependency on the amino terminus of ACE2 protein and suggests multiple epitopes on both proteins stabilize their interactions at the Nt and internal region of ACE2. In contrast, the H-CoV-NL63 RBD is only dependent on the ACE2 internal region for binding. A peptide inhibitor approach to this internal region thus far have failed to block binding of RBDs to ACE2, suggesting that several binding regions on ACE2 are sufficient to allow functional interactions. In sum, the RBD binding surface of ACE2 appears relatively fluid and amenable to bind a range of novel variants.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Rac1 Selectively Binds a Specific Lamellipodin Isoform via a Noncanonical Helical Interface 94%
- A clinically-relevant polymorphism in the Na+/taurocholate cotransporting polypeptide (NTCP) occurs at a rheostat position 94%
- Control of atypical PKC{iota} membrane dissociation by tyrosine phosphorylation within a PB1-C1 interdomain interface 94%
Similar papers in this journal
- Melanopsin Carboxy-terminus Phosphorylation Plasticity and Bulk Negative Charge, not Strict Site Specificity, Achieves Phototransduction Deactivation 93%
- Discovery of human ACE2 variants with altered recognition by the SARS-CoV-2 spike protein 93%
- Merlin Tumor Suppressor Function is Regulated by PIP2-Mediated Dimerization 93%
Similar papers in this journal
- Mutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption 94%
- Comparative analysis reveals the species-specific genetic determinants of ACE2 required for SARS-CoV-2 entry 94%
- Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2 94%
Similar papers in this journal
- Mutations affecting the N-terminal domains of SHANK3 point to different pathomechanisms in neurodevelopmental disorders. 94%
- Structural consequences of BMPR2 kinase domain mutations causing pulmonary arterial hypertension 93%
- A recombinant ACE2 Triple Decoy that traps and neutralizes SARS-CoV-2 shows enhanced affinity for highly transmissible SARS-CoV-2 variants 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.