A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans, causing COVID-19 1,2 . A key to tackling this pandemic is to understand the receptor recognition mechanism of the virus, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor-angiotensin-converting enzyme 2 (ACE2)-in humans 3,4 . Here we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2. In comparison with the SARS-CoV RBD, an ACE2-binding ridge in SARS-CoV-2 RBD has a more compact conformation; moreover, several residue changes in the SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD-ACE2 interface. These structural features of SARS-CoV-2 RBD increase its ACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus that is closely related to SARS-CoV-2, also uses human ACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in ACE2 recognition shed light on the potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies that target receptor recognition by SARS-CoV-2.The sudden emergence and rapid spread of SARS-CoV-2 is endangering global health and economy 1,2 . SARS-CoV-2 has caused many more infections, deaths and economic disruptions than SARS-CoV in 2002 . The origin of SARS-CoV-2 remains unclear. Bats are considered the original source of SARS-CoV-2 because a closely related coronavirus, RaTG13, has been isolated from bats 7 . However, the molecular events that led to the possible bat-to-human transmission of SARS-CoV-2 are unknown. Clinically approved vaccines or drugs that specifically target SARS-CoV-2 are also lacking. Receptor recognition by coronaviruses is an important determinant of viral infectivity, pathogenesis and host range 8,9 . It presents a major target for vaccination and antiviral strategies 10 . Here we elucidate the structural and biochemical mechanisms of receptor recognition by SARS-CoV-2.Receptor recognition by SARS-CoV has been extensively studied. A virus-surface spike protein mediates the entry of coronavirus into host cells. The spike protein of SARS-CoV contains a RBD that specifically recognizes ACE2 as its receptor 3,4 . A series of crystal structures of the SARS-CoV RBD from different strains in complex with ACE2 from different hosts has previously been determined 3,11,12 . These structures showed that SARS-CoV RBD contains a core and a receptor-binding motif (RBM); the RBM mediates contacts with ACE2. The surface of ACE2 contains two virus-binding hotspots that are essential for SARS-CoV binding. Several naturally selected mutations in the SARS-CoV RBM surround these hotspots and regulate the infectivity, pathogenesis, and cross-species and human-to-human transmissions of SARS-CoV 3,11,12 .Because of the sequence similarity between the spike proteins of SARS-CoV and SARS-C...

APOBEC-catalyzed cytosine-to-uracil deamination of single-stranded (ss)DNA has beneficial functions in immunity and detrimental roles in cancer. APOBEC enzymes have intrinsic dinucleotide specificities that impart hallmark mutation signatures. Despite numerous structures, mechanisms for global ssDNA recognition and local target sequence selection remain unclear. Here, we report crystal structures of human APOBEC3A and a chimera of human APOBEC3B and APOBEC3A bound to ssDNA at 3.1 and 1.7 angstroms resolution, respectively. These structures reveal a U-shaped DNA conformation, with the specificity-conferring −1 thymine flipped out and the target cytosine inserted deep into the zinc-coordinating active site pocket. The −1 thymine base fits between flexible loops in a groove that forms upon binding ssDNA, and it makes direct hydrogen bonds with the protein accounting for the strong 5′-TC preference. These studies explain both conserved and unique properties among APOBEC family members, and provide a basis for the rational design of inhibitors to impede the evolvability of viruses and tumors.

Three n-type polymers BDPPV, ClBDPPV, and FBDPPV which exhibit outstanding electrical conductivities when mixed with an n-type dopant, N-DMBI ((4-(1,3-dimethyl-2,3-dihydro-1H-benzoimidazol-2-yl)phenyl)dimethylamine), in solution. High electron mobility and an efficient doping process endow FBDPPV with the highest electrical conductivities of 14 S cm(-1) and power factors up to 28 μW m(-1) K(-2), which is the highest thermoelectric (TE) power factor that has been reported for solution processable n-type conjugated polymers. Our investigations reveal that introduction of halogen atoms to the polymer backbones has a dramatic influence on not only the electron mobilities but also the doping levels, both of which are critical to the electrical conductivities. This work suggests the significance of rational modification of polymer structures and opens the gate for applying the rapidly developed organic semiconductors with high carrier mobilities to thermoelectric field.

Many bacterial activities, including expression of virulence factors, horizontal genetic transfer, and production of antibiotics, are controlled by intercellular signaling using small molecules. To date, understanding of the molecular mechanisms of peptide-mediated cell-cell signaling has been limited by a dearth of published information about the molecular structures of the signaling components. Here, we present the molecular structure of PrgX, a DNAand peptide-binding protein that regulates expression of the conjugative transfer genes of the Enterococcus faecalis plasmid pCF10 in response to an intercellular peptide pheromone signal. Comparison of the structures of PrgX and the PrgX͞pheromone complex suggests that pheromone binding destabilizes PrgX tetramers, opening a 70-bp pCF10 DNA loop required for conjugation repression.DNA binding ͉ Gram-positive bacteria ͉ inducible conjugation ͉ x-ray crystallography ͉ transcription factor

Background: APOBEC3B-catalyzed DNA cytosine deamination causes mutations in cancer. Results: We present the first APOBEC3B catalytic domain crystal structures including a dCMP-bound form. Conclusion: A closed active site conformation distinguishes APOBEC3B from related enzymes and suggests that conformational changes are central to the overall single-stranded DNA binding mechanism. Significance: These high resolution structures provide a foundation for inhibitor development.