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-Structure paper
タイトル | Connexin-46/50 in a dynamic lipid environment resolved by CryoEM at 1.9 Å. |
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ジャーナル・号・ページ | Nat Commun, Vol. 11, Issue 1, Page 4331, Year 2020 |
掲載日 | 2020年8月28日 |
著者 | Jonathan A Flores / Bassam G Haddad / Kimberly A Dolan / Janette B Myers / Craig C Yoshioka / Jeremy Copperman / Daniel M Zuckerman / Steve L Reichow / |
PubMed 要旨 | Gap junctions establish direct pathways for cells to transfer metabolic and electrical messages. The local lipid environment is known to affect the structure, stability and intercellular channel ...Gap junctions establish direct pathways for cells to transfer metabolic and electrical messages. The local lipid environment is known to affect the structure, stability and intercellular channel activity of gap junctions; however, the molecular basis for these effects remains unknown. Here, we incorporate native connexin-46/50 (Cx46/50) intercellular channels into a dual lipid nanodisc system, mimicking a native cell-to-cell junction. Structural characterization by CryoEM reveals a lipid-induced stabilization to the channel, resulting in a 3D reconstruction at 1.9 Å resolution. Together with all-atom molecular dynamics simulations, it is shown that Cx46/50 in turn imparts long-range stabilization to the dynamic local lipid environment that is specific to the extracellular lipid leaflet. In addition, ~400 water molecules are resolved in the CryoEM map, localized throughout the intercellular permeation pathway and contributing to the channel architecture. These results illustrate how the aqueous-lipid environment is integrated with the architectural stability, structure and function of gap junction communication channels. |
リンク | Nat Commun / PubMed:32859914 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 1.9 - 2.5 Å |
構造データ | EMDB-22358: Connexin-46/50 in a dynamic lipid environment resolved by CryoEM at 1.9 angstroms EMDB-22382, PDB-7jlw: EMDB-22390, PDB-7jm9: |
化合物 | ChemComp-MC3: ChemComp-HOH: |
由来 |
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キーワード | MEMBRANE PROTEIN / Connexin / Gap Junction / Nanodisc / Lipid |