Complete topology inversion can be part of normal membrane protein biogenesis.
The topology of helical membrane proteins is generally defined during insertion of the transmembrane helices, yet it is now clear that it is possible for topology to change under unusual circumstances. It remains unclear, however, if topology reorientation is part of normal biogenesis. For dual topology dimer proteins such as the multidrug transporter EmrE, there may be evolutionary pressure to allow topology flipping so that the populations of both orientations can be equalized. We previously demonstrated that when EmrE is forced to insert in a distorted topology, topology flipping of the first transmembrane helix can occur during translation. Here, we show that topological malleability also extends to the C-terminal helix and that even complete topology inversion of the entire EmrE protein can occur after the full protein is translated and inserted. Thus, topology rearrangements are possible during normal biogenesis. Wholesale topology flipping is remarkable given the physical constraints of the membrane and expands the range of possible membrane protein folding pathways, both productive and detrimental.
Department of Chemistry and Biochemistry, UCLA-DOE Institute, Molecular Biology Institute, University of California, Los Angeles, California.
Nicholas B
NB
Woodall
Department of Chemistry and Biochemistry, UCLA-DOE Institute, Molecular Biology Institute, University of California, Los Angeles, California.
Sarah
S
Hadley
Department of Chemistry and Biochemistry, UCLA-DOE Institute, Molecular Biology Institute, University of California, Los Angeles, California.
Ying
Y
Yin
Department of Chemistry and Biochemistry, UCLA-DOE Institute, Molecular Biology Institute, University of California, Los Angeles, California.
James U
JU
Bowie
D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary
D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins
membrane protein folding; membrane topology; topology change; topology flipping; topology inversion; transmembrane helix