Premium
Endoplasmic reticulum proteins SDF 2 and SDF 2L1 act as components of the BiP chaperone cycle to prevent protein aggregation
Author(s) -
Fujimori Tsutomu,
Suno Ryoji,
Iemura Shunichiro,
Natsume Tohru,
Wada Ikuo,
Hosokawa Nobuko
Publication year - 2017
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12506
Subject(s) - endoplasmic reticulum , chaperone (clinical) , protein folding , biology , microbiology and biotechnology , chemical chaperone , unfolded protein response , foldase , calnexin , hsp70 , co chaperone , er retention , protein aggregation , mutant , biochemistry , heat shock protein , calreticulin , groel , escherichia coli , gene , medicine , pathology
The folding of newly synthesized proteins in the endoplasmic reticulum ( ER ) is assisted by ER ‐resident chaperone proteins. BiP (immunoglobulin heavy‐chain‐binding protein), a member of the HSP 70 family, plays a central role in protein quality control. The chaperone function of BiP is regulated by its intrinsic ATP ase activity, which is stimulated by ER ‐resident proteins of the HSP 40/DnaJ family, including ER dj3. Here, we report that two closely related proteins, SDF 2 and SDF 2L1, regulate the BiP chaperone cycle. Both are ER ‐resident, but SDF 2 is constitutively expressed, whereas SDF 2L1 expression is induced by ER stress. Both luminal proteins formed a stable complex with ER dj3 and potently inhibited the aggregation of different types of misfolded ER cargo. These proteins associated with non‐native proteins, thus promoting the BiP–substrate interaction cycle. A dominant‐negative ER dj3 mutant that inhibits the interaction between ER dj3 and BiP prevented the dissociation of misfolded cargo from the ER dj3– SDF 2L1 complex. Our findings indicate that SDF 2 and SDF 2L1 associate with ER dj3 and act as components in the BiP chaperone cycle to prevent the aggregation of misfolded proteins, partly explaining the broad folding capabilities of the ER under various physiological conditions.