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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Endoplasmic Reticulum, Membrane Proteins, Protein Transport, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins.
user
Is sec24 a coincidence detector that simultaneously binds two signals to drive ER export? Context: Incorporation of secretory proteins into ER-derived vesicles involves recognition of cytosolic signals by the COPII coat protein, Sec24. Additional cargo diversity is achieved through cargo receptors, which include the Erv14/Cornichon family that mediates export of transmembrane proteins despite the potential for such clients to directly interact with Sec24. The molecular function of Erv14 thus remains unclear, with possible roles in COPII binding, membrane domain chaperoning, and lipid organization. Using a targeted mutagenesis approach to define the mechanism of Erv14 function, we identify conserved residues in the second transmembrane domain of Erv14 that mediate interaction with a subset of Erv14 clients. We further show that interaction of Erv14 with a novel cargo-binding surface on Sec24 is necessary for efficient trafficking of all of its clients. However, we also determine that some Erv14 clients also directly engage an adjacent cargo-binding domain of Sec24, suggesting a novel mode of dual interaction between cargo and coat.
assistant
We conclude that Erv14 functions as a canonical cargo receptor that couples membrane proteins to the COPII coat, but that maximal export requires a bivalent signal that derives from motifs on both the cargo protein and Erv14. Sec24 can thus be considered a coincidence detector that binds simultaneously to multiple signals to drive packaging of polytopic membrane proteins. This mode of dual signal binding to a single coat protein might serve as a general mechanism to trigger efficient capture, or may be specifically employed in ER export to control deployment of nascent proteins. Final Decision: yes