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

Journal Article · Mon Jan 01 04:00:00 EST 2007 · Nature Structural and Molecular Biology

OSTI ID:930653

Wu, Z; Yan, N; Feng, L; Oberstein, A; Yan, H; Baker, R; Gu, L; Jeffrey, P; Urban, S; Shi, Y

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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 930653
• Report Number(s): BNL--81121-2008-JA
• Journal Information: Nature Structural and Molecular Biology, Journal Name: Nature Structural and Molecular Biology Journal Issue: 12 Vol. 13
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
CLEAVAGE
CRYSTAL STRUCTURE
ESCHERICHIA COLI
MEMBRANES
PEPTIDES
PROTEINS
PROTEOLYSIS
SERINE
SUBSTRATES
WATER
national synchrotron light source