Issue 4, 2021

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, which might be utilized as indicators for investigating the S1-ACE2 dynamic recognition and intervention at the molecular level in high throughput.

Graphical abstract: Probing conformational hotspots for the recognition and intervention of protein complexes by lysine reactivity profiling

Supplementary files

Article information

Article type
Edge Article
Submitted
27 Sept. 2020
Accepted
22 Nov. 2020
First published
23 Nov. 2020
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2021,12, 1451-1457

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

Z. Liu, W. Zhang, B. Sun, Y. Ma, M. He, Y. Pan and F. Wang, Chem. Sci., 2021, 12, 1451 DOI: 10.1039/D0SC05330A

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements