Chemistry

Chemical profiling of DNA G-quadruplex-interacting proteins in live cells

X. Zhang, J. Spiegel, et al.

Discover a groundbreaking co-binding-mediated protein profiling (CMPP) strategy developed by a talented team including Xiaoyun Zhang, Jochen Spiegel, Sergio Martínez Cuesta, Santosh Adhikari, and Shankar Balasubramanian. This innovative approach unveils proteins that interact with DNA G-quadruplexes in live cells, potentially leading to new insights in cellular function and disease mechanisms.

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Abstract

This paper introduces a co-binding-mediated protein profiling (CMPP) strategy to identify proteins interacting with DNA G-quadruplexes (G4s) within live cells. CMPP uses cell-permeable G4-ligand probes that bind endogenous G4s and crosslink to interacting proteins. The method's robustness was demonstrated *in vitro*, and its application in live cells identified hundreds of putative G4-interacting proteins. The G4 binding affinity and selectivity of several newly discovered interactors were confirmed *in vitro*, and direct G4 interactions were validated for a key candidate using an independent approach. This chemical strategy provides a new method for mapping protein interactions with specific nucleic acid features in living cells.

Publisher

Nature Chemistry

Published On

Jul 01, 2021

Authors

Xiaoyun Zhang, Jochen Spiegel, Sergio Martínez Cuesta, Santosh Adhikari, Shankar Balasubramanian

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