Faculty and Student Publications
Document Type
Article
Publication Date
5-12-2022
Abstract
High resolution hydroxyl radical protein footprinting (HR-HRPF) is a mass spectrometry-based method that measures the solvent exposure of multiple amino acids in a single experiment, offering constraints for experimentally informed computational modeling. HR-HRPF-based modeling has previously been used to accurately model the structure of proteins of known structure, but the technique has never been used to determine the structure of a protein of unknown structure. Here, we present the use of HR-HRPF-based modeling to determine the structure of the Ig-like domain of NRG1, a protein with no close homolog of known structure. Independent determination of the protein structure by both HR-HRPF-based modeling and heteronuclear NMR was carried out, with results compared only after both processes were complete. The HR-HRPF-based model was highly similar to the lowest energy NMR model, with a backbone RMSD of 1.6 Å. To our knowledge, this is the first use of HR-HRPF-based modeling to determine a previously uncharacterized protein structure.
Relational Format
article
Recommended Citation
Khaje, N.A., Eletsky, A., Biehn, S.E. et al. Validated determination of NRG1 Ig-like domain structure by mass spectrometry coupled with computational modeling. Commun Biol 5, 452 (2022). https://doi.org/10.1038/s42003-022-03411-y
DOI
https://doi.org/10.1038/s42003-022-03411-y
Accessibility Status
Searchable text
Comments
The Article Processing Charge (APC) for this article was partially funded by the UM Libraries Open Access Fund.