Integrating Non-NMR Distance Restraints to Augment NMR Depiction of Protein Structure and Dynamics. Issue 9 (17th April 2020)

• Record Type: Journal Article
• Authors: Tang, Chun; Gong, Zhou
• Is Part Of: Journal of molecular biology. Volume 432:Issue 9(2020)
• Page Start: 2913
• Page End: 2929
• Publication Date: 2020-04-17
• Subjects: protein dynamics -- ensemble structure refinement -- paramagnetic NMR -- single-molecule FRET (smFRET) -- chemical cross-linking coupled with mass spectrometry (CXMS); ADR ambiguous distance restraint -- BS2G bis-sulfosuccinimidyl glutarate -- BS3 bis-sulfosuccinimidyl suberate -- CEST chemical exchange saturation transfer -- CPMG Carr-Purcell-Meiboom-Gill -- cryoEM cryogenic electron microscopy -- CXMS cross-linking mass spectrometry -- DSS di-succinimidyl suberate -- EPR electron paramagnetic resonance -- FCS fluorescence correlation spectroscopy -- FRET Förster resonance energy transfer -- MBP maltose binding protein -- NMR nuclear magnetic resonance -- NOE nuclear Overhauser effect -- PCS pseudocontact shift -- PRE paramagnetic relaxation enhancement -- RDC residual dipolar coupling -- SAXS small-angle X-ray scattering -- smFRET single-molecule FRET -- SAS solvent accessible surface -- TIRF total internal reflection fluorescence; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2020.01.023
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: Nuclear magnetic resonance (NMR) structure refinement is inherently integrative. The refinement incorporates a multitude of experimental data and minimizes the difference between observed and calculated values. Here, we review how the integrative use of non-NMR measurements, in particular, distance restraints from Förster resonance energy transfer and cross-linking coupled with mass spectrometry, can augment NMR depiction of protein structure and dynamics. Refinement against both NMR and non-NMR distance restraints helps to characterize the structures of high-molecular-weight proteins and protein complexes. When a protein fluctuates among multiple conformations at millisecond or a faster timescale, NMR signals from the different conformational states may coalesce into a single set of peaks. The integration of non-NMR distance restraints facilitates the deconvolution of NMR observables to state-specific restraints. Furthermore, the integrative use of fluorescence measurements, which provides an assessment of both length scale and timescale of protein dynamics simplifies protein ensemble structure refinement otherwise with NMR restraints alone and affords a more wholesome picture of protein dynamics. Together, distance measurements are intuitive and easy to implement by using an appropriate pseudoenergy function. Future development shall involve more accurate modeling of paramagnetic and fluorescent probes, incorporation of sparse restraints from new techniques, and characterization of protein structures in a complex cellular environment. Graphical abstract: Image 1 Highlights: NMR structure refinement is inherently integrative. Refining against multiple distance restraints enables better structure depiction. Protein dynamics can be uncovered from the discrepancy in distance restraints. Single-molecule FRET helps to deconvolute ensemble-averaged NMR measurements.