Since their first identification 50 years ago, marburgviruses have emerged several times, with 83%-90% lethality in the largest outbreaks. Although no vaccines or therapeutics are available for human use, the human antibody MR191 provides complete protection in non-human primates when delivered several days after inoculation of a lethal marburgvirus dose. The detailed neutralization mechanism of MR191 remains outstanding. Here we present a 3.2 Å crystal structure of MR191 complexed with a trimeric marburgvirus surface glycoprotein (GP). MR191 neutralizes by occupying the conserved receptor-binding site and competing with the host receptor Niemann-Pick C1. The structure illuminates previously disordered regions of GP including the stalk, fusion loop, CX6CC switch, and an N-terminal region of GP2 that wraps about the outside of GP1 to anchor a marburgvirus-specific "wing" antibody epitope. Virus escape mutations mapped far outside the MR191 receptor-binding site footprint suggest a role for these other regions in the GP quaternary structure.
Pubmed ID: 29324225 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsCrystallographic software which solves structures using algorithms and automated rapid search calculations to perform molecular replacement and experimental phasing methods.
View all literature mentionsA structure-validation web application which provides an expert-system consultation about the accuracy of a macromolecular structure model, diagnosing local problems and enabling their correction. MolProbity works best as an active validation tool (used as soon as a model is available and during each rebuild/refine loop) and when used for protein and RNA crystal structures, but it may also work well for DNA, ligands and NMR ensembles. It produces coordinates, graphics, and numerical evaluations that integrate with either manual or automated use in systems such as PHENIX, KiNG, or Coot.
View all literature mentionsThis monoclonal targets MIP-1 beta
View all literature mentionsThis monoclonal targets CD16 (FcγRIII)
View all literature mentionsThis monoclonal targets CD56
View all literature mentionsThis monoclonal targets IFN-γ
View all literature mentionsThis monoclonal targets CD107a (LAMP-1)
View all literature mentionsThis monoclonal targets CD66b
View all literature mentionsThis monoclonal secondary targets IgG1 Fc
View all literature mentionsCell line FreeStyle 293-F is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Schneider 2 is a Spontaneously immortalized cell line with a species of origin Drosophila melanogaster
View all literature mentions