Identification of a SARS-like bat coronavirus that shares structural features with the spike glycoprotein receptor-binding domain of SARS-CoV-2.

SARS-CoV-2 is a recently emerged coronavirus that binds angiotensin-converting enzyme 2 (ACE2) for cell entry via its receptor-binding domain (RBD) on a surface-expressed spike glycoprotein. Studies show that despite its similarities to severe acute respiratory syndrome (SARS) coronavirus, there are critical differences in key RBD residues when compared to SARS-CoV-2. Here we present a short in silico study, showing that SARS-like bat coronavirus Rs3367 shares a high conservation with SARS-CoV-2 in important RBD residues for ACE2 binding: SARS-CoV-2's Phe486, Thr500, Asn501 and Tyr505; implicated in receptor-binding strength and host-range determination. These features were not shared with other studied bat coronaviruses belonging to the betacoronavirus genus, including RaTG13, the closest reported bat coronavirus to SARS-CoV-2's spike protein. Sequence and phylogeny analyses were followed by the computation of a reliable model of the RBD of SARS-like bat coronavirus Rs3367, which allowed structural insight of the conserved residues. Superimposition of this model on the SARS-CoV-2 ACE2-RBD complex revealed critical ACE2 contacts are also maintained. In addition, residue Asn488Rs3367 interacted with a previously defined pocket on ACE2 composed of Tyr41, Lys353 and Asp355. When compared to available SARS-CoV-2 crystal structure data, Asn501SARS-CoV-2 showed a different interaction with the ACE2 pocket. Taken together, this study offers molecular insights on RBD-receptor interactions with implications for vaccine design.

BUB-1 targets PP2A:B56 to regulate chromosome congression during meiosis I in C. elegans oocytes.

Protein Phosphatase 2A (PP2A) is a heterotrimer composed of scaffolding (A), catalytic (C), and regulatory (B) subunits. PP2A complexes with B56 subunits are targeted by Shugoshin and BUBR1 to protect centromeric cohesion and stabilise kinetochore-microtubule attachments in yeast and mouse meiosis. In Caenorhabditis elegans, the closest BUBR1 orthologue lacks the B56-interaction domain and Shugoshin is not required for meiotic segregation. Therefore, the role of PP2A in C. elegans female meiosis is unknown. We report that PP2A is essential for meiotic spindle assembly and chromosome dynamics during C. elegans female meiosis. BUB-1 is the main chromosome-targeting factor for B56 subunits during prometaphase I. BUB-1 recruits PP2A:B56 to the chromosomes via a newly identified LxxIxE motif in a phosphorylation-dependent manner, and this recruitment is important for proper chromosome congression. Our results highlight a novel mechanism for B56 recruitment, essential for recruiting a pool of PP2A involved in chromosome congression during meiosis I.