A Selective Transmembrane Recognition Mechanism by a Membrane-anchored Ubiquitin Ligase Adaptor

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2020 Dec 22

PMID 33351099

Citations 8

Authors

Felichi Mae Arines

Aaron Jeremy Hamlin

Xi Yang

Yun-Yu Jennifer Liu

Ming Li

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Arines F, Wielenga A, Stockbridge R, Li M STAR Protoc. 2024; 5(4):103483.

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Lysosomal membrane transporter purification and reconstitution for functional studies.

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An optimized protocol to analyze membrane protein degradation in yeast using quantitative western blot and flow cytometry.

Arines F, Li M STAR Protoc. 2022; 3(2):101274.

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