 |
PDBsum entry 1z0y
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Sugar binding protein
|
PDB id
|
|
|
|
1z0y
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
The structure of dc-Signr with a portion of its repeat domain lends insights to modeling of the receptor tetramer.
|
|
|
Authors
|
|
G.A.Snyder,
M.Colonna,
P.D.Sun.
|
|
|
Ref.
|
|
J Mol Biol, 2005,
347,
979-989.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The dendritic cell-specific ICAM-3 non-integrin (DC-SIGN) and its close relative
DC-SIGNR recognize various glycoproteins, both pathogenic and cellular, through
the receptor lectin domain-mediated carbohydrate recognition. While the
carbohydrate-recognition domains (CRD) exist as monomers and bind individual
carbohydrates with low affinity and are permissive in nature, the full-length
receptors form tetramers through their repeat domain and recognize specific
ligands with high affinity. To understand the tetramer-based ligand binding
avidity, we determined the crystal structure of DC-SIGNR with its last repeat
region. Compared to the carbohydrate-bound CRD structure, the structure revealed
conformational changes in the calcium and carbohydrate coordination loops of
CRD, an additional disulfide bond between the N and the C termini of the CRD,
and a helical conformation for the last repeat. On the basis of the current
crystal structure and other published structures with sequence homology to the
repeat domain, we generated a tetramer model for DC-SIGN/R using homology
modeling and propose a ligand-recognition index to identify potential receptor
ligands.
|
|
|
|
|
|
|
|
Figure 2.
Figure 2. Carbohydrate-binding and calcium-binding sites.
(a) C^a traces of the DC-SIGNR R8 (blue) and DC-SIGNR CRD (gray)
primary calcium-binding sites showing side-chains involved in
coordinating calcium. In the absence of carbohydrate, Asp377 is
not involved in calcium coordination. The calcium ion, seen in
nearly the same position in both structures is shown in yellow
(Ca2). A water molecule (red) is present in the location where
normally ligand binds (DC-SIGNR R8 structure). (b) The secondary
calcium-binding site shows the C^a loop in DCSIGNR R8 and
DC-SIGNR CRD Loop movement is observed between ligand-bound and
apo structures from closed to open, respectively. Calcium ions
present in the structure of DC-SIGNR CRD only are shown in gray
(Ca1 and Ca3). Side-chain movements between each structure are
summarized in Table 2.
|
|
Figure 4.
Figure 4. Model of the extracellular portion of the
DC-SIGN/R tetramer. (a) A side-view of the model tetramer. The
boundary of the repeat domain, CRD and carbohydrate (from
DC-SIGNR CRD PDB code 1K9J) are shown as well as a view of the
model looking down onto the top of the tetramer. (b) A single
helical tetramer model is shown with helical breaks in the
region near proline residues.
|
|
|
|
|
|
The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2005,
347,
979-989)
copyright 2005.
|
|
|
|
|
|
|
