Dimerization of ERp29, a PDI-like protein, is essential for its diverse functions.
Protein disulfide isomerase (PDI)-like proteins act as oxido-reductases and chaperones in the endoplasmic reticulum (ER). How oligomerization of the PDI-like proteins control these activities is unknown. Here we show that dimerization of ERp29, a PDI-like protein, regulates its protein unfolding and escort activities. We have demonstrated previously that ERp29 induces the local unfolding of polyomavirus in the ER, a step required for viral infection. We now find that, in contrast to wild-type ERp29, a mutant ERp29 (D42A) that dimerizes inefficiently is unable to unfold polyomavirus or stimulate infection. A compensatory mutation that partially restores dimerization to the mutant ERp29 (G37D/D42A) rescues ERp29 activity. These results indicate that dimerization of ERp29 is crucial for its protein unfolding function. ERp29 was also suggested to act as an escort factor by binding to the secretory protein thyroglobulin (Tg) in the ER, thereby facilitating its secretion. We show that this escort function likewise depends on ERp29 dimerization. Thus our data demonstrate that dimerization of a PDI-like protein acts to regulate its diverse ER activities.
Rainey-Barger
Emily K
EK
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Mkrtchian
Souren
S
Tsai
Billy
B
D016475:3T3 Cells / Q000821:virology; D000818:Animals; D002478:Cells, Cultured; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D011120:Polyomavirus / Q000472:pathogenicity; D027601:Polyomavirus Infections / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D013954:Thyroglobulin / Q000378:metabolism
C110909:Erp29 protein, rat; D006360:Heat-Shock Proteins; D013954:Thyroglobulin