Crystal Structure of a Rhomboid Family Intramembrane Protease.

Journal Article · Sun Jan 01 04:00:00 EST 2006 · Nature

DOI:https://doi.org/10.1038/nature05255· OSTI ID:930122

Wang, Y; Zhang, Y; Ha, Y

Escherichia coli GlpG is an integral membrane protein that belongs to the widespread rhomboid protease family. Rhomboid proteases, like site-2 protease (S2P) and {gamma}-secretase, are unique in that they cleave the transmembrane domain of other membrane proteins. Here we describe the 2.1 {angstrom} resolution crystal structure of the GlpG core domain. This structure contains six transmembrane segments. Residues previously shown to be involved in catalysis, including a Ser-His dyad, and several water molecules are found at the protein interior at a depth below the membrane surface. This putative active site is accessible by substrate through a large 'V-shaped' opening that faces laterally towards the lipid, but is blocked by a half-submerged loop structure. These observations indicate that, in intramembrane proteolysis, the scission of peptide bonds takes place within the hydrophobic environment of the membrane bilayer. The crystal structure also suggests a gating mechanism for GlpG that controls substrate access to its hydrophilic active site.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 930122
• Report Number(s): BNL--80767-2008-JA
• Journal Information: Nature, Journal Name: Nature Vol. 444
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
CATALYSIS
CRYSTAL STRUCTURE
DEPTH
ENVIRONMENT
ESCHERICHIA COLI
INTEGRALS
MEMBRANE PROTEINS
MEMBRANES
MOLECULES
OPENINGS
PEPTIDES
PROTEINS
PROTEOLYSIS
RESIDUES
RESOLUTION
SUBSTRATES
WATER
national synchrotron light source