scholarly journals WNK1 is an assembly factor for the human ER membrane protein complex

2021 ◽  
Author(s):  
Tino Pleiner ◽  
Masami Hazu ◽  
Giovani Pinton Tomaleri ◽  
Kurt Januszyk ◽  
Robert S. Oania ◽  
...  
Author(s):  
Tino Pleiner ◽  
Kurt Januszyk ◽  
Giovani Pinton Tomaleri ◽  
Robert S. Oania ◽  
Masami Hazu ◽  
...  

SummaryThe assembly of nascent proteins into multi-subunit complexes is tightly regulated to maintain cellular homeostasis. The ER membrane protein complex (EMC) is an essential insertase that requires seven membrane-spanning and two soluble subunits for function. Here we show that the kinase With no lysine 1 (WNK1), known for its role in hypertension and neuropathy, is required for assembly of the human EMC. WNK1 uses a conserved amphipathic helix to stabilize the soluble subunit, EMC2, by binding to the EMC2-8 interface. Shielding this hydrophobic surface prevents promiscuous interactions of unassembled EMC2 and precludes binding of ubiquitin ligases, permitting assembly. Using biochemical reconstitution, we show that after EMC2 reaches the membrane, its interaction partners within the EMC displace WNK1, and similarly shield its exposed hydrophobic surfaces. This work describes an unexpected role for WNK1 in protein biogenesis, and defines the general requirements of an assembly factor that will apply across the proteome.


2018 ◽  
Vol 132 (2) ◽  
pp. jcs223453 ◽  
Author(s):  
Norbert Volkmar ◽  
Maria-Laetitia Thezenas ◽  
Sharon M. Louie ◽  
Szymon Juszkiewicz ◽  
Daniel K. Nomura ◽  
...  

Cell Reports ◽  
2019 ◽  
Vol 27 (6) ◽  
pp. 1666-1674.e4 ◽  
Author(s):  
David L. Lin ◽  
Takamasa Inoue ◽  
Yu-Jie Chen ◽  
Aaron Chang ◽  
Billy Tsai ◽  
...  

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 624 ◽  
Author(s):  
Jeremy G. Wideman

The recently discovered endoplasmic reticulum (ER) membrane protein complex (EMC) has been implicated in ER-associated degradation (ERAD), lipid transport and tethering between the ER and mitochondrial outer membranes, and assembly of multipass ER-membrane proteins. The EMC has been studied in both animals and fungi but its presence outside the Opisthokont clade (animals + fungi + related protists) has not been demonstrated. Here, using homology-searching algorithms, I show that the EMC is truly an ancient and conserved protein complex, present in every major eukaryotic lineage. Very few organisms have completely lost the EMC, and most, even over 2 billion years of eukaryote evolution, have retained a majority of the complex members. I identify Sop4 and YDR056C in Saccharomyces cerevisiae as Emc7 and Emc10, respectively, subunits previously thought to be specific to animals. This study demonstrates that the EMC was present in the last eukaryote common ancestor (LECA) and is an extremely important component of eukaryotic cells even though its primary function remains elusive.


2020 ◽  
Vol 130 (2) ◽  
pp. 813-826 ◽  
Author(s):  
Jonathan Marquez ◽  
June Criscione ◽  
Rebekah M. Charney ◽  
Maneeshi S. Prasad ◽  
Woong Y. Hwang ◽  
...  

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 624 ◽  
Author(s):  
Jeremy G. Wideman

The recently discovered endoplasmic reticulum (ER) membrane protein complex (EMC) has been implicated in ER-associated degradation (ERAD), lipid transport and tethering between the ER and mitochondrial outer membranes, and assembly of multipass ER-membrane proteins. The EMC has been studied in both animals and fungi but its presence outside the Opisthokont clade (animals + fungi + related protists) has not been demonstrated. Here, using homology-searching algorithms, I show that the EMC is truly an ancient and conserved protein complex, present in every major eukaryotic lineage. Very few organisms have completely lost the EMC, and most, even over 2 billion years of eukaryote evolution, have retained a majority of the complex members. I identify Sop4 and YDR056C in Saccharomyces cerevisiae as Emc7 and Emc10, respectively, subunits previously thought to be specific to animals. This study demonstrates that the EMC was present in the last eukaryote common ancestor (LECA) and is an extremely important component of eukaryotic cells even though its primary function remains elusive.


PLoS ONE ◽  
2020 ◽  
Vol 15 (9) ◽  
pp. e0238435
Author(s):  
Xiong Zhu ◽  
Xin Qi ◽  
Yeming Yang ◽  
Wanli Tian ◽  
Wenjing Liu ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document