9I3R
Human TRPM4 ion channel in MAASTY copolymer lipid nanodisc in a calcium-bound state
Summary for 9I3R
| Entry DOI | 10.2210/pdb9i3r/pdb |
| EMDB information | 52611 |
| Descriptor | Transient receptor potential cation channel subfamily M member 4, CHOLESTEROL, CALCIUM ION (3 entities in total) |
| Functional Keywords | ion channel, copolymer, native nanodisc, calcium-bound, trp channel, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 543883.10 |
| Authors | Pugh, 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. (deposition date: 2025-01-23, release date: 2026-01-28) |
| Primary citation | Pugh, 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: 41372170DOI: 10.1038/s41467-025-66208-7 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.46 Å) |
Structure validation
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