SARS-CoV-2 variants with spike (S)-protein D614G mutations now predominate globally. We therefore compare the properties of the mutated S protein (SG614) with the original (SD614). We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than those with SD614. This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. Similar results are obtained with virus-like particles produced with SARS-CoV-2 M, N, E, and S proteins. However, D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion.

SARS coronavirus 2 (SARS-CoV-2) isolates encoding a D614G mutation in the viral spike (S) protein predominate over time in locales where it is found, implying that this change enhances viral transmission. We therefore compared the functional properties of the S proteins with aspartic acid (S D614 ) and glycine (S G614 ) at residue 614. We observed that retroviruses pseudotyped with S G614 infected ACE2expressing cells markedly more efficiently than those with S D614 . This greater infectivity was correlated with less S1 shedding and greater incorporation of the S protein into the pseudovirion. Similar results were obtained using the virus-like particles produced with SARS-CoV-2 M, N, E, and S proteins. However, S G614 did not bind ACE2 more efficiently than S D614 , and the pseudoviruses containing these S proteins were neutralized with comparable efficiencies by convalescent plasma.These results show S G614 is more stable than S D614 , consistent with epidemiological data suggesting that viruses with S G614 transmit more efficiently.Until late 2019, only six coronaviruses were known to infect humans: HCoV-229E, HCoV-OC43, SARS-CoV (SARS-CoV-1), HCoV-NL63, CoV-HKU1, and MERS-CoV.A seventh, SARS-CoV-2, emerged in the winter of 2019 from Wuhan, China. SARS-CoV-2 is closely related to SARS-CoV-1, a virus that appeared from Guangdong province, China in late 2002.The coronavirus spike (S) protein mediates receptor binding and fusion of the viral and cellular membrane. The S protein extends from the viral membrane and is uniformly arranged as trimers on the virion surface to give the appearance of a crown (corona in

The F-actin binding cytoskeletal protein α-catenin interacts with β-catenin-cadherin complexes and stabilizes cell-cell junctions. The β-catenin–α-catenin complex cannot bind to F-actin, whereas interactions of α-catenin with the cytoskeletal protein vinculin appear necessary to stabilize adherens junctions. Here we report the crystal structure of nearly full-length human α-catenin at 3.7 Å resolution. α-Catenin forms an asymmetric dimer, where the four-helix bundle domains of each subunit engage in distinct intermolecular interactions. This results in a left handshake-like dimer, where the two subunits have remarkably different conformations. The crystal structure explains why dimeric α-catenin has a higher affinity for F-actin than monomeric α-catenin, why the β-catenin–α-catenin complex does not bind to F-actin, how activated vinculin links the cadherin-catenin complex to the cytoskeleton, and why α-catenin but not inactive vinculin can bind to F-actin.

PIP2 binds vinculin and directs its oligomerization, which promotes proper focal adhesion structure and function.

Background: ␣-Catenin provides links for cadherin receptors to the actin cytoskeleton at cell-cell adherens junctions. Results: Extensive ␣-catenin interactions with vinculin are displaced by the vinculin tail domain. Conclusion: ␣-Catenin-vinculin interactions are stabilized by F-actin. Significance: The data support a new model whereby vinculin activation at adherens junctions is sufficient to stabilize connections of ␣-catenin with the actin network.