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TitlepH-tunable membrane-active polymers, NCMNP2a-, and their potential membrane protein applications.
Journal, issue, pagesChem Sci, Vol. 14, Issue 26, Page 7310-7326, Year 2023
Publish dateJul 5, 2023
AuthorsThi Kim Hoang Trinh / Andres Jorge Cabezas / Soumil Joshi / Claudio Catalano / Abu Bakkar Siddique / Weihua Qiu / Sanket Deshmukh / Amedee des Georges / Youzhong Guo /
PubMed AbstractAccurate 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 ...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-. The results demonstrated that NCMNP2a- could be used for high-resolution single-particle cryo-EM structural analysis of AcrB in various pH conditions and can effectively solubilize TSPO 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- might have broad applications in membrane protein research.
External linksChem Sci / PubMed:37416719 / PubMed Central
MethodsEM (single particle)
Resolution3.05 - 3.51 Å
Structure data

24653

7rr6

EMDB-24653, PDB-7rr6:
Multidrug efflux pump subunit AcrB
Method: EM (single particle) / Resolution: 3.1 Å

24654

7rr7

EMDB-24654, PDB-7rr7:
Multidrug efflux pump subunit AcrB
Method: EM (single particle) / Resolution: 3.05 Å

24655

7rr8

EMDB-24655, PDB-7rr8:
Multidrug efflux pump subunit AcrB
Method: EM (single particle) / Resolution: 3.51 Å

Chemicals

ChemComp-PTY:
PHOSPHATIDYLETHANOLAMINE / phospholipid*YM

ChemComp-D12:
DODECANE

Source
  • escherichia coli (strain k12) (bacteria)
KeywordsTRANSPORT PROTEIN / Multidrug efflux pump subunit AcrB / NCMN

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