Structure-based vaccine design depends on extensive structural analyses of antigen-antibody complexes.Single-particle electron cryomicroscopy (cryoEM) can circumvent some of the problems of x-ray crystallography as a pipeline for obtaining the required structures. We have examined the potential of single-particle cryoEM for determining the structure of influenza-virus hemagglutinin (HA):single-chain variable-domain fragment complexes, by studying a complex we failed to crystallize in pursuing an extended project on the human immune response to influenza vaccines.The result shows that a combination of cryoEM and molecular modeling can yield details of the antigen-antibody interface, although small variation in the twist of the rod-likeHA trimer limited the overall resolution to about 4.5Å.Comparison of principal 3D classes suggests ways to modify the HA trimer to overcome this limitation. A closely related antibody from the same donor did yield crystals when bound with the same HA, giving us an independent validation of the cryoEM results.The two structures also augment our understanding of receptor-binding site recognition by antibodies that neutralize a wide range of influenza-virus variants.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535819 | PMC |
| http://dx.doi.org/10.1016/j.jmb.2017.05.011 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Phages adapt to recognize an O-antigen polysaccharide site by mutating the 'backup' tail protein ORF59, enabling reinfection of phage-resistant .
Emerg Microbes Infect
January 2025
College of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou, China.
Phages demonstrate remarkable promise as antimicrobial agents against antibiotic-resistant bacteria. However, the emergence of phage-resistant strains poses challenges to their effective application. In this paper, we presented the isolation of a phage adaptive mutant that demonstrated enhanced and sustained antibacterial efficacy through the co-evolution of () 111-2 and phage ZX1Δint .
View Article and Find Full Text PDFStructural and Functional Glycosylation of the Abdala COVID-19 Vaccine.
Glycobiology
January 2025
Department of Biochemistry, Dorothy Crowfoot Hodgkin Building, University of Oxford, South Parks Road, OX1 3QU, United Kingdom.
Abdala is a COVID-19 vaccine produced in Pichia pastoris and is based on the receptor-binding domain (RBD) of the SARS-CoV-2 spike. Abdala is currently approved for use in multiple countries with clinical trials confirming its safety and efficacy in preventing severe illness and death. Although P.
View Article and Find Full Text PDFCharacterization and Fluctuations of an Ivermectin Binding Site at the Lipid Raft Interface of the N-Terminal Domain (NTD) of the Spike Protein of SARS-CoV-2 Variants.
Viruses
November 2024
Department of Biology, Faculty of Medicine, Aix-Marseille University, INSERM UA16, 13015 Marseille, France.
Most studies on the docking of ivermectin on the spike protein of SARS-CoV-2 concern the receptor binding domain (RBD) and, more precisely, the RBD interface recognized by the ACE2 receptor. The N-terminal domain (NTD), which controls the initial attachment of the virus to lipid raft gangliosides, has not received the attention it deserves. In this study, we combined molecular modeling and physicochemical approaches to analyze the mode of interaction of ivermectin with the interface of the NTD-facing lipid rafts of the host cell membrane.
View Article and Find Full Text PDFCharacterization of Site-Specific N- and O-Glycopeptides from Recombinant Spike and ACE2 Glycoproteins Using LC-MS/MS Analysis.
Int J Mol Sci
December 2024
Digital Omics Research Center, Korea Basic Science Institute, Ochang 28119, Republic of Korea.
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in hundreds of millions of infections and millions of deaths globally. Although vaccination campaigns are mitigating the pandemic, emerging viral variants continue to pose challenges. The spike (S) protein of SARS-CoV-2 plays a critical role in viral entry by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, making both proteins essential targets for therapeutic and vaccine development.
View Article and Find Full Text PDFUnderstanding Folding of bFGF and Potential Cellular Protective Mechanisms of Neural Cells.
Biochemistry
January 2025
Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland 20742, United States.
Article Synopsis
- Traumatic brain injury (TBI) affects many individuals, especially veterans and athletes, and has serious, long-term consequences for brain health.
- Current research explores the role of fibroblast growth factor (FGF) proteins in protecting cells, highlighting knowledge gaps regarding how heparin and similar molecules activate bFGF and how mutations affect its stability.
- Using temperature replica exchange, the study identified a new binding site on bFGF and revealed that various sugars affect bFGF interactions similarly to heparin, underscoring the need for a deeper understanding of TBI mechanisms for better treatment development.
Want 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!