Crystal structure of a rhomboid family intramembrane protease - PubMed (original) (raw)
. 2006 Nov 9;444(7116):179-80.
doi: 10.1038/nature05255. Epub 2006 Oct 11.
Affiliations
- PMID: 17051161
- DOI: 10.1038/nature05255
Crystal structure of a rhomboid family intramembrane protease
Yongcheng Wang et al. Nature. 2006.
Abstract
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 A 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.
Comment in
- Structural biology: enzyme theory holds water.
Freeman M. Freeman M. Nature. 2006 Nov 9;444(7116):153-5. doi: 10.1038/nature05305. Nature. 2006. PMID: 17051148 No abstract available.
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