Using Cross‐Correlated Spin Relaxation to Characterize Backbone Dihedral Angle Distributions of Flexible Protein Segments. Issue 1 (10th December 2020)

• Record Type: Journal Article
• Authors: Kauffmann, Clemens; Zawadzka‐Kazimierczuk, Anna; Kontaxis, Georg; Konrat, Robert
• Is Part Of: Chemphyschem. Volume 22:Issue 1(2021)
• Page Start: 18
• Page End: 28
• Publication Date: 2020-12-10
• Subjects: cross-correlated relaxation -- NMR spectroscopy -- protein dynamics -- protein structures -- statistical inference; Chemistry, Physical and theoretical -- Periodicals; 541.05
• DOI: 10.1002/cphc.202000789
• Languages: English
• ISSNs: 1439-4235

Abstract

Abstract: Crucial to the function of proteins is their existence as conformational ensembles sampling numerous and structurally diverse substates. Despite this widely accepted notion there is still a high demand for meaningful and reliable approaches to characterize protein ensembles in solution. As it is usually conducted in solution, NMR spectroscopy offers unique possibilities to address this challenge. Particularly, cross‐correlated relaxation (CCR) effects have long been established to encode both protein structure and dynamics in a compelling manner. However, this wealth of information often limits their use in practice as structure and dynamics might prove difficult to disentangle. Using a modern Maximum Entropy (MaxEnt) reweighting approach to interpret CCR rates of Ubiquitin, we demonstrate that these uncertainties do not necessarily impair resolving CCR‐encoded structural information. Instead, a suitable balance between complementary CCR experiments and prior information is found to be the most crucial factor in mapping backbone dihedral angle distributions. Experimental and systematic deviations such as oversimplified dynamics appear to be of minor importance. Using Ubiquitin as an example, we demonstrate that CCR rates are capable of characterizing rigid and flexible residues alike, indicating their unharnessed potential in studying disordered proteins. Abstract : Cross‐correlated spin relaxation (CCR) rates uniquely encode both protein structure and dynamics but their quantitative interpretation is challenging in the presence of conformational heterogeneity. Using a Maximum Entropy approach, we demonstrate that CCR rates are capable of characterizing dihedral angle distributions of both rigid and flexible residues in Ubiquitin.