5kyx

From Proteopedia

crystal structure of Sec23 and TANGO1 peptide1 complex

PDB ID 5kyx

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Structural highlights

5kyx is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.516Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SC23A_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]

Function

SC23A_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 PubMed

The supramolecular cargo procollagen is loaded into coat protein complex II (COPII)-coated carriers at endoplasmic reticulum (ER) exit sites by the receptor molecule TANGO1/cTAGE5. Electron microscopy studies have identified a tubular carrier of suitable dimensions that is molded by a distinctive helical array of the COPII inner coat protein Sec23/24*Sar1; the helical arrangement is absent from canonical COPII-coated small vesicles. In this study, we combined X-ray crystallographic and biochemical analysis to characterize the association of TANGO1/cTAGE5 with COPII proteins. The affinity for Sec23 is concentrated in the proline-rich domains (PRDs) of TANGO1 and cTAGE5, but Sec23 recognizes merely a PPP motif. The PRDs contain repeated PPP motifs separated by proline-rich linkers, so a single TANGO1/cTAGE5 receptor can bind multiple copies of coat protein in a close-packed array. We propose that TANGO1/cTAGE5 promotes the accretion of inner coat proteins to the helical lattice. Furthermore, we show that PPP motifs in the outer coat protein Sec31 also bind to Sec23, suggesting that stepwise COPII coat assembly will ultimately displace TANGO1/cTAGE5 and compartmentalize its operation to the base of the growing COPII tubule.

TANGO1/cTAGE5 receptor as a polyvalent template for assembly of large COPII coats.,Ma W, Goldberg J Proc Natl Acad Sci U S A. 2016 Sep 6;113(36):10061-6. doi:, 10.1073/pnas.1605916113. Epub 2016 Aug 22. PMID:27551091^[2]

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

References

↑ Boyadjiev SA, Fromme JC, Ben J, Chong SS, Nauta C, Hur DJ, Zhang G, Hamamoto S, Schekman R, Ravazzola M, Orci L, Eyaid W. Cranio-lenticulo-sutural dysplasia is caused by a SEC23A mutation leading to abnormal endoplasmic-reticulum-to-Golgi trafficking. Nat Genet. 2006 Oct;38(10):1192-7. Epub 2006 Sep 17. PMID:16980979 doi:10.1038/ng1876
↑ Ma W, Goldberg J. TANGO1/cTAGE5 receptor as a polyvalent template for assembly of large COPII coats. Proc Natl Acad Sci U S A. 2016 Sep 6;113(36):10061-6. doi:, 10.1073/pnas.1605916113. Epub 2016 Aug 22. PMID:27551091 doi:http://dx.doi.org/10.1073/pnas.1605916113