While it is well-known that E3 ubiquitin ligases can selectively ubiquitinate membrane proteins in response to specific environmental cues, the underlying mechanisms for the selectivity are poorly understood. In particular, the role of transmembrane regions, if any, in target recognition remains an open question. Here, we describe how Ssh4, a yeast E3 ligase adaptor, recognizes the PQ-loop lysine transporter Ypq1 only after lysine starvation. We show evidence of an interaction between two transmembrane helices of Ypq1 (TM5 and TM7) and the single transmembrane helix of Ssh4. This interaction is regulated by the conserved PQ motif. Strikingly, recent structural studies of the PQ-loop family have suggested that TM5 and TM7 undergo major conformational changes during substrate transport, implying that transport-associated conformational changes may determine the selectivity. These findings thus provide critical information concerning the regulatory mechanism through which transmembrane domains can be specifically recognized in response to changing environmental conditions.
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4 January 2021
Article|
December 22 2020
A selective transmembrane recognition mechanism by a membrane-anchored ubiquitin ligase adaptor
Felichi Mae Arines
,
Felichi Mae Arines
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI
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Aaron Jeremy Hamlin
,
Aaron Jeremy Hamlin
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI
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Xi Yang
,
Xi Yang
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI
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Yun-Yu Jennifer Liu
,
Yun-Yu Jennifer Liu
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI
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Ming Li
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI
Correspondence to Ming Li: mlium@umich.edu
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Felichi Mae Arines
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI
Aaron Jeremy Hamlin
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI
Yun-Yu Jennifer Liu
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI
Correspondence to Ming Li: mlium@umich.edu
Received:
January 19 2020
Revision Received:
September 10 2020
Accepted:
October 30 2020
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding:
Cystinosis Research Foundation
(CRFF-2018-005)
MCubed, University of Michigan
(NO AWARD)
National Institutes of Health
(R01GM133873)
© 2020 Arines et al.
2020
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2021) 220 (1): e202001116.
Article history
Received:
January 19 2020
Revision Received:
September 10 2020
Accepted:
October 30 2020
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Citation
Felichi Mae Arines, Aaron Jeremy Hamlin, Xi Yang, Yun-Yu Jennifer Liu, Ming Li; A selective transmembrane recognition mechanism by a membrane-anchored ubiquitin ligase adaptor. J Cell Biol 4 January 2021; 220 (1): e202001116. doi: https://doi.org/10.1083/jcb.202001116
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