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The retrograde cargo receptor Erv41-Erv46 retrieves non–KDEL-bearing ER resident proteins to maintain ER homeostasis. This study defines a conserved cysteine-rich element in Erv46 that is required for retrieval activity and cargo binding. We propose that disulfides within the cysteine-rich region regulate the hydrophobic cargo binding site.

Molecular dissection of the Erv41-Erv46 retrograde receptor reveals a conserved cysteine-rich region in Erv46 required for retrieval activity