 |
PDBsum entry 2cm4
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
The structure of omci, A novel lipocalin inhibitor of the complement system.
|
|
|
Authors
|
|
P.Roversi,
O.Lissina,
S.Johnson,
N.Ahmat,
G.C.Paesen,
K.Ploss,
W.Boland,
M.A.Nunn,
S.M.Lea.
|
|
|
Ref.
|
|
J Mol Biol, 2007,
369,
784-793.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
|
|
|
|
Abstract
|
|
|
The complement (C) system is a potent innate immune defence system against
parasites. We have recently characterised and expressed OmCI, a 16 kDa protein
derived from the soft tick Ornithodoros moubata that specifically binds C5,
thereby preventing C activation. The structure of recombinant OmCI determined at
1.9 A resolution confirms a lipocalin fold and reveals that the protein binds a
fatty acid derivative that we have identified by mass spectrometry as ricinoleic
acid. We propose that OmCI could sequester one of the fatty acid-derived
inflammatory modulators from the host plasma, thereby interfering with the host
inflammatory response to the tick bite. Mapping of sequence differences between
OmCI and other tick lipocalins with different functions, combined with
biochemical investigations of OmCI activity, supports the hypothesis that OmCI
acts by preventing interaction with the C5 convertase, rather than by blocking
the C5a cleavage site.
|
|
|
|
|
|
|
|
Figure 1.
Figure 1. (a) Cartoon representations of the OmCI molecule
from the P2[1]2[1]2[1]-A crystal form. Colour: blue to red, from
N terminus to C terminus. The cysteine side-chains and the
ricinoleic acid ligand are shown in stick representation, with C
atoms coloured orange, O red and S green. The strands and
helices are labelled following the tick lipocalin
nomenclature.^36 (b) OmCI molecular surface coloured by
electrostatic potential, in the same orientations as in (a).
Contours: − 2 kT/e, red; + 2 kT/e, blue. The pictures were
produced with the PyMol [http://www.pymol.sourceforge.net/]. The
electrostatic potential was computed with the program APBS^42,
run within PyMol, with the following parameters: ε[protein] =
2.0; ε[solvent] = 78.0; ionic strength, 150 mM NaCl. In (a) and
(b), views 1 and 2 are rotated by 90° around the horizontal
axis.
|
|
Figure 3.
Figure 3. (a) P2[1]2[1]2[1]-A 1.9 Å F[o]–F[c]
electron density, contoured at the + 3.0 σ level, computed
before any modelling of the ligand was attempted. The final
model for the ricinoleic acid ligand is shown with C (orange)
and O(red) surrounded by the OmCI pocket residues (C, green; O,
red; N, blue; and S, yellow); the picture was produced with
PyMol [http://www.pymol.sourceforge.net/]. (b) A representation
of the water molecules and OmCI residues forming hydrogen bonds
(with distances in Å) and non-bonding hydrophobic contacts
to the ricinoleic acid. The picture was produced with the
program LigPLot.^57
|
|
|
|
|
|
The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2007,
369,
784-793)
copyright 2007.
|
|
|
|
|
|
|
