PDBsum entry 2nrf

Membrane protein

PDB id: 2nrf

Contents

Protein chains

182 a.a. *

173 a.a. *

Waters ×26

* Residue conservation analysis

PDB id:

2nrf

Name:

Membrane protein

Title:

Crystal structure of glpg, a rhomboid family intramembrane protease

Structure:

Protein glpg. Chain: a, b. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Gene: glpg. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.60Å R-factor: 0.285 R-free: 0.295

Authors:

Z.Wu,N.Yan,L.Feng,H.Yan,L.Gu,Y.Shi

Key ref:

Z.Wu et al. (2006). Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry. Nat Struct Mol Biol, 13, 1084-1091. PubMed id: 17099694 DOI: 10.1038/nsmb1179

Date:

02-Nov-06 Release date: 14-Nov-06

Protein chain

P09391  (GLPG_ECOLI) -  Rhomboid protease GlpG from Escherichia coli (strain K12)

Seq: 276 a.a.

Struc: 182 a.a.

Protein chain

P09391  (GLPG_ECOLI) -  Rhomboid protease GlpG from Escherichia coli (strain K12)

Seq: 276 a.a.

Struc: 173 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.3.4.21.105 - rhomboid protease.

DOI no: 10.1038/nsmb1179

Nat Struct Mol Biol 13:1084-1091 (2006)

PubMed id: 17099694

Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry.

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

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 alpha4 approximately 10 A 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 alpha5 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 alpha5.

Selected figure(s)

Figure 3.
Figure 3. Conformation of the active site and the L1 loop. (a) Ribbon diagram of GlpG (molecule A) showing the open cavity leading to the active site. All invariant residues among the eight rhomboid homologs in Figure 2 are shown. Red side chains, putative catalytic-dyad residues Ser201 and His254; gold side chains, all other invariant residues; red spheres, three water molecules in the cavity. Ser201 hydrogen-bonds to His254 as well as a water molecule. (b) Stereo view of interactions surrounding the conserved Trp-Arg motif in GlpG. Trp136 and Arg137 appear to stabilize the conformation of the L1 loop by participating in a network of hydrogen bonds as well as van der Waals interactions with surrounding residues of the L1 loop. (c) Stereo view of packing interactions between residues of the L1 loop and residues in helix 3 and the L3 loop. This interface is dominated by extensive van der Waals interactions. (d) Stereo comparison of packing interactions involving the L1 loop in our structure and in that reported recently^24. Coloring of our structure is as in a except that all side chains are colored yellow. The main chain and side chains of the published structure^24 are in gray. The structure and the packing interactions are nearly identical between these two structures.

Figure 6.
Figure 6. A proposed general mechanism for intramembrane proteases. In this model, presenilin, S2P and signal-peptide peptidase may each contain a water cavity that opens to the cytoplasm or extracellular region. As in rhomboid GlpG, this water-accessible cavity is probably protected from the hydrophobic lipid bilayer by -helices and embedded loops. Before catalysis, one or more of the surrounding helices undergoes a structural switch that opens a lateral gate to allow entry of substrate protein. Star denotes active site.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2006, 13, 1084-1091) copyright 2006.

Figures were selected by an automated process.