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-Structure paper
| タイトル | DeFrND: detergent-free reconstitution into native nanodiscs with designer membrane scaffold peptides. |
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| ジャーナル・号・ページ | Nat Commun, Vol. 16, Issue 1, Page 7973, Year 2025 |
| 掲載日 | 2025年8月26日 |
著者 | Qian Ren / Jing Wang / Vinay Idikuda / Shanwen Zhang / Jeehae Shin / W Grant Ludlam / Luis M Real Hernandez / Sara Zdancewicz / Alex J B Kreutzberger / Hucheng Chang / Volker Kiessling / Lukas K Tamm / Ahmad Jomaa / Ilya Levental / Kirill Martemyanov / Baron Chanda / Huan Bao / ![]() |
| PubMed 要旨 | Membrane scaffold protein-based nanodiscs have facilitated unprecedented structural and biophysical analysis of membrane proteins in a near-native lipid environment. However, successful ...Membrane scaffold protein-based nanodiscs have facilitated unprecedented structural and biophysical analysis of membrane proteins in a near-native lipid environment. However, successful reconstitution of membrane proteins in nanodiscs requires prior solubilization and purification in detergents, which may impact their physiological structure and function. Furthermore, the detergent-mediated reconstitution of nanodiscs is unlikely to recapitulate the precise composition or asymmetry of native membranes. To circumvent this fundamental limitation of traditional nanodisc technology, we herein describe the development of membrane-solubilizing peptides to directly extract membrane proteins from native cell membranes into nanoscale discoids. By systematically protein engineering and screening, we create a class of chemically modified Apolipoprotein-A1 mimetic peptides to enable the formation of detergent-free nanodiscs with high efficiency. Nanodiscs generated with these engineered membrane scaffold peptides are suitable for obtaining high-resolution structures using single-particle cryo-EM with native lipids. To further highlight the versatility of our approach, we directly extract a sampling of membrane signaling proteins with their surrounding native membranes for biochemical and biophysical interrogations. |
リンク | Nat Commun / PubMed:40858559 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.26 - 3.51 Å |
| 構造データ | EMDB-44435, PDB-9bcr: EMDB-49659, PDB-9nqj: EMDB-49901, PDB-9nxc: |
| 化合物 | ![]() ChemComp-MG: ![]() ChemComp-ADP: ![]() ChemComp-VO4: |
| 由来 |
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キーワード | TRANSPORT PROTEIN / bacterial prototype ATP-binding cassette transporter |
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