2017
DOI: 10.1038/s41598-017-08522-9
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Structure formation during translocon-unassisted co-translational membrane protein folding

Abstract: Correctly folded membrane proteins underlie a plethora of cellular processes, but little is known about how they fold. Knowledge of folding mechanisms centres on reversible folding of chemically denatured membrane proteins. However, this cannot replicate the unidirectional elongation of the protein chain during co-translational folding in the cell, where insertion is assisted by translocase apparatus. We show that a lipid membrane (devoid of translocase components) is sufficient for successful co-translational… Show more

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Cited by 51 publications
(114 citation statements)
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“…This in turn has simplified the description of the ‘second stage’ of folding, at which the already inserted helices pack together 2730 . Current models assuming that the topology is completely fixed may need to accommodate more degrees of topological freedom of the unfolded state 22,31 . In that respect, better understanding of how common these phenomena are is crucial.…”
Section: Discussionmentioning
confidence: 99%
“…This in turn has simplified the description of the ‘second stage’ of folding, at which the already inserted helices pack together 2730 . Current models assuming that the topology is completely fixed may need to accommodate more degrees of topological freedom of the unfolded state 22,31 . In that respect, better understanding of how common these phenomena are is crucial.…”
Section: Discussionmentioning
confidence: 99%
“…bR is the best characterized with respect to folding studies, with far-UV CD indicating a significant reduction in helicity (21,23) and DEER suggesting a smaller reduction in helix structure and more or less complete loss of helix, helix tertiary interactions (59). Less direct information is available for SDS denatured states of other proteins that have been the subject of unfolding studies; for example, GlpG in SDS exhibits no loss of helical structure and very little change in fluorescence emission band, which in any case is challenging to assign to definitive structural change (10,60,61).…”
Section: H2omentioning
confidence: 99%
“…Equally, lipids can induce posttranslational repositioning of helices and protein orientation within the membrane (6,7). If the unique folded state is an equilibrium structure, then it should be possible to achieve the folded structure via other pathways, as has been demonstrated for example from coexpression (8), from reassembly of protein fragments (9), or from cell-free synthesis (10). Moreover, it has proved possible to regain the folded structure of some membrane proteins from a partly denatured state in urea, by refolding directly into liposomes (11).…”
mentioning
confidence: 99%
“…The majority of work on membrane protein folding uses relatively well-behaved proteins that have been purified following cellular overexpression and partially unfolded in a denaturant. A significant amount of structure remains in this unfolded state [9,11,[14][15][16][17][18][19][20]. While still providing valuable information, particularly for example with regard to thermodynamics, it is unclear precisely how this in vitro reversible folding relates to co-translational folding in the cell, in which insertion and folding occur during polypeptide synthesis ( Fig.…”
Section: Why Study Nascent Chain Folding?mentioning
confidence: 99%