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Publication Abstract from PubMed

Zinc ions (Zn(2+)) are imported into the early secretory pathway by Golgi-resident transporters, but their handling and functions are not fully understood. Here, we show that Zn(2+) binds with high affinity to the pH-sensitive chaperone ERp44, modulating its localization and ability to retrieve clients like Ero1alpha and ERAP1 to the endoplasmic reticulum (ER). Silencing the Zn(2+) transporters that uptake Zn(2+) into the Golgi led to ERp44 dysfunction and increased secretion of Ero1alpha and ERAP1. High-resolution crystal structures of Zn(2+)-bound ERp44 reveal that Zn(2+) binds to a conserved histidine-cluster. The consequent large displacements of the regulatory C-terminal tail expose the substrate-binding surface and RDEL motif, ensuring client capture and retrieval. ERp44 also forms Zn(2+)-bridged homodimers, which dissociate upon client binding. Histidine mutations in the Zn(2+)-binding sites compromise ERp44 activity and localization. Our findings reveal a role of Zn(2+) as a key regulator of protein quality control at the ER-Golgi interface.

Zinc regulates ERp44-dependent protein quality control in the early secretory pathway.,Watanabe S, Amagai Y, Sannino S, Tempio T, Anelli T, Harayama M, Masui S, Sorrentino I, Yamada M, Sitia R, Inaba K Nat Commun. 2019 Feb 5;10(1):603. doi: 10.1038/s41467-019-08429-1. PMID:30723194^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.