The insertase YidC chaperones the polytopic membrane protein MelB inserting and folding simultaneously from both termini
Abstract
The insertion and folding of proteins into membranes is crucial for cell viability. Yet, the detailed contributions of insertases remain elusive. Here, we monitor how the insertase YidC guides the folding of the polytopic melibiose permease MelB into membranes. In vivo experiments using conditionally depleted E. coli strains show that MelB can insert in the absence of SecYEG if YidC resides in the cytoplasmic membrane. In vitro single-molecule force spectroscopy reveals that the MelB substrate itself forms two folding cores from which structural segments insert stepwise into the membrane. However, misfolding dominates, particularly in structural regions that interface the pseudo-symmetric α-helical domains of MelB. Here, YidC takes an important role in accelerating and chaperoning the stepwise insertion and folding process of both MelB folding cores. Our findings reveal a great flexibility of the chaperoning and insertase activity of YidC in the multifaceted folding processes of complex polytopic membrane proteins. Show more
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https://doi.org/10.3929/ethz-b-000640073Publication status
publishedExternal links
Journal / series
StructureVolume
Pages / Article No.
Publisher
Cell PressSubject
atomic force microscopy; single-molecule force spectroscopy; insertase; YidC; E.coli; MelB; membrane protein insertion and folding; misfolding; folding pathways; folding domainsFunding
182587 - Characterizing the cell cycle dependent regulation of adhesion to extracellular matrix proteins (SNF)
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