Validated Determination of NRG1 Ig-like Domain Structure by Mass Spectrometry Coupled with Computational Modeling

Overview

Journal Commun Biol

Specialty Biology

Date 2022 May 13

PMID 35551273

Authors

Niloofar Abolhasani Khaje

Alexander Eletsky

Sarah E Biehn

Charles K Mobley

Monique J Rogals

Yoonkyoo Kim

Sushil K Mishra

Robert J Doerksen

Steffen Lindert

James H Prestegard

Joshua S Sharp

Affiliations

Soon will be listed here.

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.

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