pH-tunable membrane-active polymers, NCMNP2a-x, and their potential membrane protein applications

Thi Kim Hoang Trinh, Andres Jorge Cabezas, Soumil Joshi, Claudio Catalano, Abu Bakkar Siddique, Weihua Qiu, Sanket Deshmukh, Amedee des Georges, Youzhong Guo

Research output: Contribution to journalArticlepeer-review


Accurate 3D structures of membrane proteins are essential for comprehending their mechanisms of action and designing specific ligands to modulate their activities. However, these structures are still uncommon due to the involvement of detergents in the sample preparation. Recently, membrane-active polymers have emerged as an alternative to detergents, but their incompatibility with low pH and divalent cations has hindered their efficacy. Herein, we describe the design, synthesis, characterization, and application of a new class of pH-tunable membrane-active polymers, NCMNP2a-x. The results demonstrated that NCMNP2a-x could be used for high-resolution single-particle cryo-EM structural analysis of AcrB in various pH conditions and can effectively solubilize BcTSPO with the function preserved. Molecular dynamic simulation is consistent with experimental data that shed great insights into the working mechanism of this class of polymers. These results demonstrated that NCMNP2a-x might have broad applications in membrane protein research.

Original languageEnglish (US)
Pages (from-to)7310-7326
Number of pages17
JournalChemical Science
Issue number26
StatePublished - Jun 9 2023

ASJC Scopus subject areas

  • General Chemistry


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