Insertion and folding pathways of single membrane proteins guided by translocases and insertases

Science Advances
Tetiana SerdiukDaniel J Müller

Abstract

Biogenesis in prokaryotes and eukaryotes requires the insertion of α-helical proteins into cellular membranes for which they use universally conserved cellular machineries. In bacterial inner membranes, insertion is facilitated by YidC insertase and SecYEG translocon working individually or cooperatively. How insertase and translocon fold a polypeptide into the native protein in the membrane is largely unknown. We apply single-molecule force spectroscopy assays to investigate the insertion and folding process of single lactose permease (LacY) precursors assisted by YidC and SecYEG. Both YidC and SecYEG initiate folding of the completely unfolded polypeptide by inserting a single structural segment. YidC then inserts the remaining segments in random order, whereas SecYEG inserts them sequentially. Each type of insertion process proceeds until LacY folding is complete. When YidC and SecYEG cooperate, the folding pathway of the membrane protein is dominated by the translocase. We propose that both of the fundamentally different pathways along which YidC and SecYEG insert and fold a polypeptide are essential components of membrane protein biogenesis.

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Citations

Aug 25, 2020·Biochemical Society Transactions·Andrea Marco AmatiChristoph von Ballmoos
May 4, 2021·Frontiers in Molecular Biosciences·Julia OswaldHans-Georg Koch
Aug 27, 2019·Langmuir : the ACS Journal of Surfaces and Colloids·Kanokporn ChattrakunGavin M King
Aug 22, 2021·Journal of Molecular Biology·Rafayel PetrosyanMichael T Woodside
Sep 25, 2021·Nature Reviews. Molecular Cell Biology·Ramanujan S Hegde, Robert J Keenan
Dec 8, 2021·Nature Communications·Pawel R LaskowskiDaniel J Müller
Dec 17, 2021·BMC Biology·Aaron J O Lewis, Ramanujan S Hegde

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Methods Mentioned

BETA
atomic force microscopy
AFM
electrophoresis
transmission

Software Mentioned

SecYEG
YidC

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