Dimerization of ERp29, a PDI-like protein, is essential for its diverse functions

• Published in: Molecular biology of the cell Vol. 18; no. 4; pp. 1253 - 1260
• Main Authors: Rainey-Barger, Emily K, Mkrtchian, Souren, Tsai, Billy
• Format: Journal Article
• Language: English
• Published: United States The American Society for Cell Biology 01.04.2007
• Subjects: 3T3 Cells - virology; Animals; Cells, Cultured; Dimerization; Endoplasmic Reticulum - metabolism; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Medicin och hälsovetenskap; Mice; Mutation; Polyomavirus - pathogenicity; Polyomavirus Infections - metabolism; Protein Structure, Tertiary; Rats; Thyroglobulin - metabolism; Thyroglobulin - secretion
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.E06-11-1004

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.