5vnm | pdb_00005vnm
Crystal structure of Sec23a/Sec24a/Sec22 complexed with 4-phenylbutyric acid (15mM soaking)
Structural highlights
DiseaseSC23A_HUMAN Defects in SEC23A are the cause of craniolenticulosutural dysplasia (CLSD) [MIM:607812; also known as cranio-lenticulo-sutural dysplasia. CLSD is an autosomal recessive syndrome characterized by late-closing fontanels, sutural cataracts, facial dysmorphisms and skeletal defects.[1] FunctionSC23A_HUMAN Component of the COPII coat, that covers ER-derived vesicles involved in transport from the endoplasmic reticulum to the Golgi apparatus. COPII acts in the cytoplasm to promote the transport of secretory, plasma membrane, and vacuolar proteins from the endoplasmic reticulum to the Golgi complex. Publication Abstract from PubMedNative 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. ER retention is imposed by COPII protein sorting and attenuated by 4-phenylbutyrate.,Ma W, Goldberg E, Goldberg J Elife. 2017 Jun 8;6. pii: e26624. doi: 10.7554/eLife.26624. PMID:28594326[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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