AbstractThe outbreak of coronavirus disease (COVID-19) in China caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. It is currently no specific viral protein targeted therapeutics yet. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein is yet to be clear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although overall structure is similar with other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the β-sheet core. Complemented by in vitro binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.
Increased planting densities have boosted maize yields. Upright plant architecture facilitates dense planting. Here, we cloned UPA1 (Upright Plant Architecture1) and UPA2, two quantitative trait loci conferring upright plant architecture. UPA2 is controlled by a two-base sequence polymorphism regulating the expression of a B3-domain transcription factor (ZmRAVL1) located 9.5 kilobases downstream. UPA2 exhibits differential binding by DRL1 (DROOPING LEAF1), and DRL1 physically interacts with LG1 (LIGULELESS1) and represses LG1 activation of ZmRAVL1. ZmRAVL1 regulates brd1 (brassinosteroid C-6 oxidase1), which underlies UPA1, altering endogenous brassinosteroid content and leaf angle. The UPA2 allele that reduces leaf angle originated from teosinte, the wild ancestor of maize, and has been lost during maize domestication. Introgressing the wild UPA2 allele into modern hybrids and editing ZmRAVL1 enhance high-density maize yields.
SignificanceFlowering time is a critical determinant of crop adaptation to local environments. As a result of natural and artificial selection, maize has evolved a reduced photoperiod sensitivity to adapt to regions over 90° of latitude in the Americas. Here we show that a distant Harbinger-like transposon acts as a cis-regulatory element to repress ZmCCT9 expression to promote flowering under the long days of higher latitudes. The transposon at ZmCCT9 and another functional transposon at a second flowering-time gene, ZmCCT10, arose sequentially following domestication and were targeted by selection as maize spread from the tropics to higher latitudes. Our results demonstrate that new functional variation created by transposon insertions helped maize to spread over a broad range of latitudes rapidly.
Dysregulated immune cell responses have been linked to the severity of coronavirus disease 2019 (COVID-19), but the specific viral factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were currently unknown. Herein, we reveal that the Ig-like fold ectodomain of the viral protein SARS-CoV-2 ORF7a interacts with high efficiency to CD14
+
monocytes in human peripheral blood, compared to pathogenic protein SARS-CoV ORF7a. The crystal structure of SARS-CoV-2 ORF7a at 2.2 Å resolution reveals three remarkable changes on the amphipathic side of the four-stranded β-sheet, implying a potential functional interface of the viral protein. Importantly, SARS-CoV-2 ORF7a coincubation with CD14
+
monocytes
ex vivo
triggered a decrease in HLA-DR/DP/DQ expression levels and upregulated significant production of proinflammatory cytokines, including IL-6, IL-1β, IL-8, and TNF-α. Our work demonstrates that SARS-CoV-2 ORF7a is an immunomodulating factor for immune cell binding and triggers dramatic inflammatory responses, providing promising therapeutic drug targets for pandemic COVID-19.
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