3b45
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Crystal structure of GlpG at 1.9A resolution
OverviewOverview
Intramembrane proteases are important enzymes in biology. The recently, solved crystal structures of rhomboid protease GlpG have provided useful, insights into the mechanism of these membrane proteins. Besides revealing, an internal water-filled cavity that harbored the Ser-His catalytic dyad, the crystal structure identified a novel structural domain (L1 loop) that, lies on the side of the transmembrane helices. Here, using site-directed, mutagenesis, we confirmed that the L1 loop is partially embedded in the, membrane, and showed that alanine substitution of a highly preferred, tryptophan (Trp136) at the distal tip of the L1 loop near the lipid:water, interface reduced GlpG proteolytic activity. Crystallographic analysis, showed that W136A mutation did not modify the structure of the protease., Instead, the polarity for a small and lipid-exposed protein surface at the, site of the mutation has changed. The crystal structure, now refined at, 1.7 A resolution, also clearly defined a 20-A-wide hydrophobic belt around, the protease, which likely corresponded to the thickness of the compressed, membrane bilayer around the protein. This improved structural model, predicts that all critical elements of the catalysis, including the, catalytic serine and the L5 cap, need to be positioned within a few, angstroms of the membrane surface, and may explain why the protease, activity is sensitive to changes in the protein:lipid interaction. Based, on these findings, we propose a model where the end of the substrate, transmembrane helix first partitions out of the hydrophobic core region of, the membrane before it bends into the protease active site for cleavage.
About this StructureAbout this Structure
3B45 is a Single protein structure of sequence from Escherichia coli with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
The role of L1 loop in the mechanism of rhomboid intramembrane protease GlpG., Wang Y, Maegawa S, Akiyama Y, Ha Y, J Mol Biol. 2007 Dec 7;374(4):1104-13. Epub 2007 Oct 11. PMID:17976648
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