Co-Translational Folding of the First Transmembrane Domain of ABC-Transporter CFTR is Supported by Assembly with the First Cytosolic Domain

Bertrand Kleizen,Marcel van Willigen,Marjolein Mijnders,Florence Peters,Magda Grudniewska,Tamara Hillenaar,Ann Thomas,Laurens Kooijman,Kathryn W Peters,Raymond Frizzell,Peter van der Sluijs,Ineke Braakman

Journal of Molecular Biology（2021）

引用 26|浏览9

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摘要

•Folding of polytopic multispanning membrane proteins: mechanism facilitates fidelity.•Co-translational packing of TMD1 N-C-termini with ICL1, independent of other domains.•TMD1 packing improved by assembly with (even misfolded) NBD1.•TMD1 packing is limiting factor in CFTR folding: VX-809 enhances, additive to NBD1.•Likely conserved early assembly of first two domains sets path for successful folding.

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关键词

protein folding,domain assembly,helical packing,co-translational,multispanning membrane proteins

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