The spike (S) protein of SARS-CoV-2 mediates receptor binding and cell entry and is the dominant target of the immune system. It exhibits substantial conformational flexibility. It transitions from closed to open conformations to expose its receptor-binding site and, subsequently, from prefusion to postfusion conformations to mediate fusion of viral and cellular membranes. S-protein derivatives are components of vaccine candidates and diagnostic assays, as well as tools for research into the biology and immunology of SARS-CoV-2. Here we have designed mutations in S that allow the production of thermostable, disulfide-bonded S-protein trimers that are trapped in the closed, prefusion state. Structures of the disulfide-stabilized and non-disulfide-stabilized proteins reveal distinct closed and locked conformations of the S trimer. We demonstrate that the designed, thermostable, closed S trimer can be used in serological assays. This protein has potential applications as a reagent for serology, virology and as an immunogen.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116388 | PMC |
| http://dx.doi.org/10.1038/s41594-020-0478-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Recent advancements in the diverse roles of polymerase-associated proteins in the replication and pathogenesis of Newcastle disease virus.
Vet Res
January 2025
Key Laboratory of Animal Genetics, Breeding and Reproduction in The Plateau Mountainous Region, Ministry of Education, Guizhou University, Guiyang, 550025, China.
Newcastle disease virus (NDV) is a significant member of the Paramyxoviridae family, known for causing epidemics and substantial economic losses in the poultry industry worldwide. The NDV RNA genome primarily encodes six structural proteins (N, P, M, F, HN, and L) and two non-structural proteins (V and W). Among these, the polymerase-associated proteins (N, P, and L) and the viral RNA (vRNA) genome form the ribonucleoprotein complex, which plays a crucial role in the synthesis and transcription of NDV vRNA.
View Article and Find Full Text PDFHighly Active Carbonic Anhydrase of the Thylakoid Lumen of .
Plants (Basel)
December 2024
Institute of Basic Biological Problems, Federal Research Center "Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences", 142290 Pushchino, Russia.
The green unicellular algae contains 12-13 carbonic anhydrases (CAs). For a long time, the two closely related α-CAs of the periplasmic membrane CAH1 and CAH2 were considered to be the CAs with the highest CO hydration activity. The recombinant protein α-CA CAH3 (rCAH3) from the thylakoid lumen obtained in the present study showed more than three times higher activity compared to CAH1 and more than 11 times higher compared to previous studies with rCAH3.
View Article and Find Full Text PDFSynthesis and Reactivity of an Olefin Metathesis-Catalyzing Ruthenium Complex with a Selenoether Moiety in the Benzylidene Ligand.
ACS Omega
December 2024
Division of Materials Science, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma, Nara 630-0192, Japan.
A Hoveyda-Grubbs (HG)-type olefin metathesis complex with a selenoether moiety at the terminus of phenoxy moiety was synthesized. The complex showed direct selenium-atom coordination to the ruthenium center, resulting in higher thermodynamic stability compared with the parent HG catalyst. The selenium atom binding enhanced the tolerance to protic solvent molecules in ring-closing metathesis of -tosyldiallylamide and diethyl diallylmalonate, and also in the cross metathesis between 3-butenylbenzoate and methyl acrylate.
View Article and Find Full Text PDFSF3B1 thermostability as an assay for splicing inhibitor interactions.
J Biol Chem
December 2024
Department of Molecular Cell and Developmental Biology, University of California, Santa Cruz, California, USA; Center for Molecular Biology of RNA, University of California, Santa Cruz, California, USA. Electronic address:
The spliceosome protein, SF3B1 associates with U2 snRNP during early spliceosome assembly for pre-mRNA splicing. Frequent somatic mutations in SF3B1 observed in cancer necessitates characterization of its role in identifying the branchpoint adenosine of introns. Remarkably, SF3B1 is the target of three distinct natural product drugs, each identified by their potent anti-tumor properties.
View Article and Find Full Text PDFDesign of ancestral mammalian alkaline phosphatase bearing high stability and productivity.
Appl Environ Microbiol
December 2024
Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan.
Unlabelled: Mammalian alkaline phosphatase (AP) is widely used in diagnostics and molecular biology but its widespread use is impaired because it is difficult to express in and has low thermostability. To overcome these challenges, we employed sequence-based protein redesign methods, specifically full consensus design (FCD) and ancestral sequence reconstruction (ASR), to create APs with enhanced properties. Biochemical analyses revealed that these newly designed APs exhibited improved levels of expression in their active form and increased thermostability compared to bovine intestinal AP isozyme II (bIAPII), without impeding enzymatic activity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!