Probing conformational hotspots for the recognition and intervention of protein complexes by lysine reactivity profiling.

ABSTRACT: Probing the conformational and functional hotspot sites within aqueous native protein complexes is still a challenging task. Herein, a mass spectrometry (MS)-based two-step isotope labeling-lysine reactivity profiling (TILLRP) strategy is developed to quantify the reactivities of lysine residues and probe the molecular details of protein-protein interactions as well as evaluate the conformational interventions by small-molecule active compounds. The hotspot lysine sites that are crucial to the SARS-CoV-2 S1-ACE2 combination could be successfully probed, such as S1 Lys⁴¹⁷ and Lys⁴⁴⁴. Significant alteration of the reactivities of lysine residues at the interaction interface of S1-RBD Lys³⁸⁶-Lys⁴⁶² was observed during the formation of complexes, whi

SUBMITTER: Liu Z 

PROVIDER: S-EPMC8179027 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature