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Title: Structrural Analysis of a Rhomboid Family Intramembrane Protease Reveals a Gating Mechanism for Substrate Entry

Abstract

Intramembrane proteolysis regulates diverse biological processes. Cleavage of substrate peptide bonds within the membrane bilayer is catalyzed by integral membrane proteases. Here we report the crystal structure of the transmembrane core domain of GlpG, a rhomboid-family intramembrane serine protease from Escherichia coli. The protein contains six transmembrane helices, with the catalytic Ser201 located at the N terminus of helix {alpha}4 approximately 10 Angstroms below the membrane surface. Access to water molecules is provided by a central cavity that opens to the extracellular region and converges on Ser201. One of the two GlpG molecules in the asymmetric unit has an open conformation at the active site, with the transmembrane helix {alpha}5 bent away from the rest of the molecule. Structural analysis suggests that substrate entry to the active site is probably gated by the movement of helix {alpha}5.

Authors:
; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
930653
Report Number(s):
BNL-81121-2008-JA
TRN: US200901%%164
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nature Structural and Molecular Biology; Journal Volume: 13; Journal Issue: 12
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; CLEAVAGE; CRYSTAL STRUCTURE; ESCHERICHIA COLI; MEMBRANES; PEPTIDES; PROTEINS; PROTEOLYSIS; SERINE; SUBSTRATES; WATER; national synchrotron light source

Citation Formats

Wu,Z., Yan, N., Feng, L., Oberstein, A., Yan, H., Baker, R., Gu, L., Jeffrey, P., Urban, S., and Shi, Y. Structrural Analysis of a Rhomboid Family Intramembrane Protease Reveals a Gating Mechanism for Substrate Entry. United States: N. p., 2007. Web.
Wu,Z., Yan, N., Feng, L., Oberstein, A., Yan, H., Baker, R., Gu, L., Jeffrey, P., Urban, S., & Shi, Y. Structrural Analysis of a Rhomboid Family Intramembrane Protease Reveals a Gating Mechanism for Substrate Entry. United States.
Wu,Z., Yan, N., Feng, L., Oberstein, A., Yan, H., Baker, R., Gu, L., Jeffrey, P., Urban, S., and Shi, Y. Mon . "Structrural Analysis of a Rhomboid Family Intramembrane Protease Reveals a Gating Mechanism for Substrate Entry". United States. doi:.
@article{osti_930653,
title = {Structrural Analysis of a Rhomboid Family Intramembrane Protease Reveals a Gating Mechanism for Substrate Entry},
author = {Wu,Z. and Yan, N. and Feng, L. and Oberstein, A. and Yan, H. and Baker, R. and Gu, L. and Jeffrey, P. and Urban, S. and Shi, Y.},
abstractNote = {Intramembrane proteolysis regulates diverse biological processes. Cleavage of substrate peptide bonds within the membrane bilayer is catalyzed by integral membrane proteases. Here we report the crystal structure of the transmembrane core domain of GlpG, a rhomboid-family intramembrane serine protease from Escherichia coli. The protein contains six transmembrane helices, with the catalytic Ser201 located at the N terminus of helix {alpha}4 approximately 10 Angstroms below the membrane surface. Access to water molecules is provided by a central cavity that opens to the extracellular region and converges on Ser201. One of the two GlpG molecules in the asymmetric unit has an open conformation at the active site, with the transmembrane helix {alpha}5 bent away from the rest of the molecule. Structural analysis suggests that substrate entry to the active site is probably gated by the movement of helix {alpha}5.},
doi = {},
journal = {Nature Structural and Molecular Biology},
number = 12,
volume = 13,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}