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9SMK

Human TRPM4 ion channel in MSP2N2 lipid nanodisc in a calcium-bound state

Summary for 9SMK
Entry DOI10.2210/pdb9smk/pdb
EMDB information55036
DescriptorTransient receptor potential cation channel subfamily M member 4, CALCIUM ION, CHOLESTEROL HEMISUCCINATE (3 entities in total)
Functional Keywordsion channel, msp nanodisc, calcium-bound, trpm4, membrane protein
Biological sourceHomo sapiens (human)
Total number of polymer chains4
Total formula weight545083.96
Authors
Primary citationPugh, C.F.,Feilen, L.P.,Zivkovic, D.,Praestegaard, K.F.,Sideris, C.,Borthwick, N.J.,de Lichtenberg, C.,Bolla, J.R.,Autzen, A.A.A.,Autzen, H.E.
MAASTY: a (dis)ordered copolymer for structural determination of human membrane proteins in native nanodiscs.
Nat Commun, 16:11399-11399, 2025
Cited by
PubMed Abstract: Amphiphilic copolymers capable of extracting membrane proteins directly from cellular membranes into "native nanodiscs" offer a simplified approach for preparing membrane proteins in lipid nanodiscs compared to approaches that rely on detergent. Copolymer amphiphilicity, length, and composition influence their performance, in addition to the protein itself and the purification conditions used. Here, we report a copolymer composed of methacrylic acid and styrene, which we term MAASTY, leveraging the inherent monomer reactivity ratios to create an anionic copolymer with a statistical distribution of monomers. We show that MAASTY can be used for high-resolution structural determination of a human membrane protein by single particle cryo-electron microscopy, preserving endogenous lipids including cholesterol and exhibiting an enrichment of phosphatidylinositol. Moreover, MAASTY copolymers effectively solubilize a broad range of lipid species and a wide range of different, eukaryotic membrane proteins from mammalian cells. We find that MAASTY copolymers are promising as effective solubilizers of membrane proteins and offer a chemical platform for structural and functional characterization of membrane proteins in native nanodiscs.
PubMed: 41372170
DOI: 10.1038/s41467-025-66208-7
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.8 Å)
Structure validation

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