Extending the detectable time window of fast protein dynamics using (1)H(N) E-CPMG

利用 (1)H(N) E-CPMG 扩展快速蛋白质动力学的可检测时间窗口

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Abstract

Recent advances in high power NMR relaxation dispersion experiments have significantly enhanced our ability to study fast µs timescale motions in proteins, which are crucial for understanding their biological functions. Here, we have extended the detectable time window of such fast dynamics with the development of extreme power (1)H Carr-Purcell-Meiboom-Gill ((1)H E-CPMG) experiments targeted at the backbone amide protons ((1)H(N)). Using this methodology, artifact-free relaxation dispersion profiles can be obtained up to extreme pulsing conditions with minimal setup effort using commonly used standard NMR hardware. We demonstrate the utility of ¹H E-CPMG on human ubiquitin, revealing that the previously reported peptide flip motion influences a larger region of the protein backbone than previously recognized. Additionally, we directly observed a faster dynamic process at residue T09, aligning with previously predicted pincer mode motion. These findings underscore the effectiveness of (1)H E-CPMG in extending the temporal resolution at which biologically relevant fast protein dynamics can be studied.

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