skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Insights into COPll 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{center_dot}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{center_dot}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.

Authors:
; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
960135
Report Number(s):
BNL-83121-2009-JA
TRN: US201016%%1279
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Developmental Cell; Journal Volume: 13
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; CONVERGENCE; CRYSTAL STRUCTURE; ENDOPLASMIC RETICULUM; HYDROLYSIS; MUTATIONS; NUCLEATION; POLYPEPTIDES; PROTEINS; RESIDUES; national synchrotron light source

Citation Formats

Bi,X., Mancias, J., and Goldberg, J. Insights into COPll Coat Nucleation from the Structure of Sec23 Sar1 Complexed with the Active Fragment of Sec31. United States: N. p., 2007. Web. doi:10.1016/j.devcel.2007.10.006.
Bi,X., Mancias, J., & Goldberg, J. Insights into COPll Coat Nucleation from the Structure of Sec23 Sar1 Complexed with the Active Fragment of Sec31. United States. doi:10.1016/j.devcel.2007.10.006.
Bi,X., Mancias, J., and Goldberg, J. Mon . "Insights into COPll Coat Nucleation from the Structure of Sec23 Sar1 Complexed with the Active Fragment of Sec31". United States. doi:10.1016/j.devcel.2007.10.006.
@article{osti_960135,
title = {Insights into COPll Coat Nucleation from the Structure of Sec23 Sar1 Complexed with the Active Fragment of Sec31},
author = {Bi,X. and Mancias, J. and Goldberg, J.},
abstractNote = {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{center_dot}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{center_dot}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.},
doi = {10.1016/j.devcel.2007.10.006},
journal = {Developmental Cell},
number = ,
volume = 13,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}