 |
PDBsum entry 2nrf
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Membrane protein
|
PDB id
|
|
|
|
2nrf
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry.
|
|
|
Authors
|
|
Z.Wu,
N.Yan,
L.Feng,
A.Oberstein,
H.Yan,
R.P.Baker,
L.Gu,
P.D.Jeffrey,
S.Urban,
Y.Shi.
|
|
|
Ref.
|
|
Nat Struct Mol Biol, 2006,
13,
1084-1091.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
