Protein quality control is crucial for maintaining cellular homeostasis and its dysfunction is closely linked to human diseases. The post-translational protein quality control machinery mainly composed of BCL-2-associated athanogene 6 (BAG6) is responsible for triage of mislocalized membrane proteins (MLPs). However, it is unknown how the BAG6-mediated degradation of MLPs is regulated. We report here that PAQR9, a member of the Progesterone and AdipoQ receptor (PAQR) family, is able to modulate BAG6-mediated triage of MLPs. Analysis with mass spectrometry identified that BAG6 is one of the major proteins interacting with PAQR9 and such interaction is confirmed by co-immunoprecipitation and co-localization assays. The protein degradation rate of representative MLPs is accelerated by PAQR9 knockdown. Consistently, the polyubiquitination of MLPs is enhanced by PAQR9 knockdown. PAQR9 binds to the DUF3538 domain within the proline-rich stretch of BAG6. PAQR9 reduces the binding of MLPs to BAG6 in a DUF3538 domain-dependent manner. Taken together, our results indicate that PAQR9 plays a role in the regulation of protein quality control of MLPs via affecting the interaction of BAG6 with membrane proteins.
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Prevotella intermedia PinO protein is homologous to Porphyromonas gingivalis HmuY hemophore-like protein, but binds haem with a different haem coordination mode and preferentially in reducing environment. Molecular dynamics stimulations of the haem iron coordination by the PinO suggest engagement of one methionine residue, with interchangeable participation of two additional methionine residues. For more information, see the article by Bielecki and colleagues on pp. 381–405. Image courtesy of Teresa Olczak.
PAQR9 Modulates BAG6-mediated protein quality control of mislocalized membrane proteins
Xue You, Yijun Lin, Yongfan Hou, Lijiao Xu, Qianqian Cao, Yan Chen; PAQR9 Modulates BAG6-mediated protein quality control of mislocalized membrane proteins. Biochem J 31 January 2020; 477 (2): 477–489. doi: https://doi.org/10.1042/BCJ20190620
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