Insights into COPII coat nucleation from the structure of Sec23•Sar1 complexed with the active fragment of Sec31 Journal Article
| Authors: | Bi, X.; Mancias, J. D.; Goldberg, J. |
| Article Title: | Insights into COPII coat nucleation from the structure of Sec23•Sar1 complexed with the active fragment of Sec31 |
| Abstract: | The COPII vesicular coat forms on the endoplasmic reticulum from Sar1-GTP, Sec23/24 and Sec13/31 protein subunits. Here, we define the interaction between Sec23/24•Sar1 and Sec13/31, involving a 40 residue Sec31 fragment. In the crystal structure of the ternary complex, Sec31 binds as an extended polypeptide across a composite surface of the Sec23 and Sar1-GTP molecules, explaining the stepwise character of Sec23/24•Sar1 and Sec13/31 recruitment to the membrane. The Sec31 fragment stimulates GAP activity of Sec23/24, and a convergence of Sec31 and Sec23 residues at the Sar1 GTPase active site explains how GTP hydrolysis is triggered leading to COPII coat disassembly. The Sec31 active fragment is accommodated in a binding groove supported in part by Sec23 residue Phe380. Substitution of the corresponding residue F382L in human Sec23A causes cranio-lenticulo-sutural dysplasia, and we suggest that this mutation disrupts the nucleation of COPII coat proteins at endoplasmic reticulum exit sites. © 2007 Elsevier Inc. All rights reserved. |
| Keywords: | controlled study; unclassified drug; gene mutation; pathogenesis; nonhuman; protein conformation; animal cell; complex formation; amino acid substitution; protein assembly; protein protein interaction; cell protein; protein binding; endoplasmic reticulum; amino acid sequence; molecular sequence data; cell membrane; cellbio; guanosine triphosphatase activating protein; binding site; crystal structure; models, molecular; crystallography, x-ray; binding sites; protein structure; leucine; guanosine triphosphate; hydrolysis; phenylalanine; enzyme active site; vesicular transport proteins; monomeric gtp-binding proteins; coat protein complex ii; cop-coated vesicles; craniofacial malformation; cytoplasm protein; protein sar1; protein sec13; protein sec23; protein sec24; protein sec31; craniolenticulosutural dysplasia |
| Journal Title: | Developmental Cell |
| Volume: | 13 |
| Issue: | 5 |
| ISSN: | 1534-5807 |
| Publisher: | Cell Press |
| Date Published: | 2007-11-01 |
| Start Page: | 635 |
| End Page: | 645 |
| Language: | English |
| DOI: | 10.1016/j.devcel.2007.10.006 |
| PUBMED: | 17981133 |
| PROVIDER: | scopus |
| PMCID: | PMC2686382 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 44" - "Export Date: 17 November 2011" - "CODEN: DCEEB" - "Source: Scopus" |
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