 |
PDBsum entry 1d2s
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transport protein
|
PDB id
|
|
|
|
1d2s
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Crystal structure of human sex hormone-Binding globulin: steroid transport by a laminin g-Like domain.
|
|
|
Authors
|
|
I.Grishkovskaya,
G.V.Avvakumov,
G.Sklenar,
D.Dales,
G.L.Hammond,
Y.A.Muller.
|
|
|
Ref.
|
|
EMBO J, 2000,
19,
504-512.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Human sex hormone-binding globulin (SHBG) transports sex steroids in blood and
regulates their access to target tissues. In biological fluids, SHBG exists as a
homodimer and each monomer comprises two laminin G-like domains (G domains). The
crystal structure of the N-terminal G domain of SHBG in complex with
5alpha-dihydrotestosterone at 1.55 A resolution reveals both the architecture of
the steroid-binding site and the quaternary structure of the dimer. We also show
that G domains have jellyroll topology and are structurally related to
pentraxin. In each SHBG monomer, the steroid intercalates into a hydrophobic
pocket within the beta-sheet sandwich. The steroid and a 20 A distant calcium
ion are not located at the dimer interface. Instead, two separate
steroid-binding pockets and calcium-binding sites exist per dimer. The structure
displays intriguing disorder for loop segment Pro130-Arg135. In all other
jellyroll proteins, this loop is well ordered. If modelled accordingly, it
covers the steroid-binding site and could thereby regulate access of ligands to
the binding pocket.
|
|
|
|
|
|
|
|
Figure 2.
Figure 2 The G domain fold in SHBG. (A and B) Ribbon
representation of the N-terminal domain of SHBG in two
orthogonal orientations. The  -strands
of the two sheets forming a -sandwich
are coloured in yellow and blue, respectively. The steroid 5
 -DHT
is shown in a ball and stick representation. The segment
130–135, which is expected to loop over the steroid-binding
pocket, is disordered and not visible in the electron density.
The calcium ion is shown as a green dot (figures generated with
MOLSCRIPT and RASTER3D; Kraulis, 1991; Merritt and Murphy,
1994). (C) Topology diagram of the -strands.
Triangles pointing upwards denote -strands
pointing out of the paper plane. The conserved disulfide bond
between residues 164 and 188 is indicated as a dashed line.
|
|
Figure 3.
Figure 3 (A) Ribbon representation of the human SHBG dimer
coloured according to the atomic displacement factors
(temperature factors) and model for the packing of the
C-terminal G domains (in grey). The displacement factors range
from 12 (dark blue) to 55 Å^2 (red). (B) Stereo
representation of the steroid-binding pocket in an orientation
identical to that in Figure 2B. All side chains that are in
contact with the steroid are displayed. (C) Chemical structure
and atom numbering in 5 -DHT.
In testosterone, a double bond is present between atoms C4 and
C5. In oestradiol, ring A is aromatic, C19 is missing and the
carbonyl oxygen at C3 is replaced by a hydroxyl group.
|
|
|
|
|
|
The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2000,
19,
504-512)
copyright 2000.
|
|
|
|
|
|
|
