Complete topology inversion can be part of normal membrane protein biogenesis.

Autor: Woodall NB; Department of Chemistry and Biochemistry, UCLA-DOE Institute, Molecular Biology Institute, University of California, Los Angeles, California., Hadley S; Department of Chemistry and Biochemistry, UCLA-DOE Institute, Molecular Biology Institute, University of California, Los Angeles, California., Yin Y; Department of Chemistry and Biochemistry, UCLA-DOE Institute, Molecular Biology Institute, University of California, Los Angeles, California., Bowie JU; Department of Chemistry and Biochemistry, UCLA-DOE Institute, Molecular Biology Institute, University of California, Los Angeles, California.
Jazyk: angličtina
Zdroj: Protein science : a publication of the Protein Society [Protein Sci] 2017 Apr; Vol. 26 (4), pp. 824-833. Date of Electronic Publication: 2017 Feb 25.
DOI: 10.1002/pro.3131
Abstrakt: 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.
(© 2017 The Protein Society.)
Databáze: MEDLINE
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