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Media type:
E-Article
Title:
Transmembrane segments of nascent polytopic membrane proteins control cytosol/ER targeting during membrane integration
Contributor:
Lin, Pen-Jen;
Jongsma, Candice G.;
Liao, Shuren;
Johnson, Arthur E.
Published:
Rockefeller University Press, 2011
Published in:
Journal of Cell Biology, 195 (2011) 1, Seite 41-54
Language:
English
DOI:
10.1083/jcb.201103117
ISSN:
1540-8140;
0021-9525
Origination:
Footnote:
Description:
During cotranslational integration of a eukaryotic multispanning polytopic membrane protein (PMP), its hydrophilic loops are alternately directed to opposite sides of the ER membrane. Exposure of fluorescently labeled nascent PMP to the cytosol or ER lumen was detected by collisional quenching of its fluorescence by iodide ions localized in the cytosol or lumen. PMP loop exposure to the cytosol or lumen was controlled by structural rearrangements in the ribosome, translocon, and associated proteins that occurred soon after a nascent chain transmembrane segment (TMS) entered the ribosomal tunnel. Each successive TMS, although varying in length, sequence, hydrophobicity, and orientation, reversed the structural changes elicited by its predecessor, irrespective of loop size. Fluorescence lifetime data revealed that TMSs occupied a more nonpolar environment than secretory proteins inside the aqueous ribosome tunnel, which suggests that TMS recognition by the ribosome involves hydrophobic interactions. Importantly, the TMS-triggered structural rearrangements that cycle nascent chain exposure between cytosolic and lumenal occur without compromising the permeability barrier of the ER membrane.