5VNI

Crystal structure of Sec23a/Sec24a/Sec22 complexed with a C-terminal FA sorting motif

Summary for 5VNI

• Entry DOI: 10.2210/pdb5vni/pdb
• Related: 5VNE 5VNF 5VNG 5VNH 5VNJ 5VNK 5VNL 5VNM 5VNN 5VNO
• Descriptor: Protein transport protein Sec23A, Protein transport protein Sec24A, Vesicle-trafficking protein SEC22b, ... (6 entities in total)
• Functional Keywords: copii, trafficking, p24, er retention, protein transport
• Biological source: Homo sapiens (Human); More
• Cellular location: Smooth endoplasmic reticulum membrane; Peripheral membrane protein: Q15436; Cytoplasm : O95486; Endoplasmic reticulum membrane ; Single-pass type IV membrane protein : O08547
• Total number of polymer chains: 4
• Total formula weight: 189201.28

Authors

Ma, W.,Goldberg, J. (deposition date: 2017-04-30, release date: 2017-07-05, Last modification date: 2023-10-04)

Primary citation

Ma, W.,Goldberg, E.,Goldberg, J.
ER retention is imposed by COPII protein sorting and attenuated by 4-phenylbutyrate.
Elife, 6:-, 2017

PubMed Abstract: Native cargo proteins exit the endoplasmic reticulum (ER) in COPII-coated vesicles, whereas resident and misfolded proteins are substantially excluded from vesicles by a retention mechanism that remains unresolved. We probed the ER retention process using the proteostasis regulator 4-phenylbutyrate (4-PBA), which we show targets COPII protein to reduce the stringency of retention. 4-PBA competes with p24 proteins to bind COPII. When p24 protein uptake is blocked, COPII vesicles package resident proteins and an ER-trapped mutant LDL receptor. We further show that 4-PBA triggers the secretion of a KDEL-tagged luminal resident, implying that a compromised retention mechanism causes saturation of the KDEL retrieval system. The results indicate that stringent ER retention requires the COPII coat machinery to actively sort biosynthetic cargo from diffusible misfolded and resident ER proteins.

PubMed: 28594326
DOI: 10.7554/eLife.26624

Experimental method

X-RAY DIFFRACTION (2.788 Å)