Chemistry Reference
In-Depth Information
As mentioned above, the Ca
2+
-dependent glycoprotein cargo transporter ERGIC-
53 (p58) in animals is another
-sandwich protein. This intracellular lectin has
two cation-binding sites, but only one can be set into obvious structural relation
to the constellation of the respective Ca
2+
-binding section present in leguminous
lectins (Figure 16.1c). However, the detected structural changes upon complex-
ation are reminiscent of those in the mentioned plant proteins, and the selection
of complex mannose structures as ligands by ERGIC-53 (please see Chapter 6 for
details) may have actually required the intramolecular shift of one site [5] . Of note,
the yeast orthologs of ERGIC-53, that is Emp47p and Emp46p, accomplish their
mission as glycan cargo receptors without dependence on Ca
2+
, as the proteins of
the galectin family (please see Figures 13.2/13.3 for folding and ligand binding,
Chapter 19, for example Table 19.2, for information on functions and Table 19.3
for listing of ligands) and carbohydrate-binding modules (CBM) of polysaccharide-
degrading microbial enzymes (CBM families 4, 6 and 22) constitute further cases
for Ca
2+
- independent
β
-sandwich lectins [6-8]. Evidently, this type of scaffold has
turned out to be a highly fl exible platform for lectin generation, and this multi-
purpose character goes along with broadening the role of Ca
2+
in ligand binding.
By turning to the pentraxins (phylogenetically conserved proteins arranged into a
disk - like structure of fi ve non-covalently associated protomers), the next aspect of
Ca
2+
functionality will be profi led.
β
Figure 16.1
Illustration of X - ray crystallographic
evidence [with the Protein Data Bank (PDB)
codes] for the functional versatility of Ca
2+
in lec-
tins. In each case, the general folding of the lec-
tin (left) and the anatomy of the Ca
2+
- binding
site(s) or carbohydrate recognition domain
(CRD) including the crucial Ca
2+
with, if avail-
able, the sugar ligand (right) are presented:
Ca
2+
-loaded ConA in complex with Man
α
1 -
3Man (a; 1DQO), the luminal domain of the
canine lectin chaperone calnexin (b; 1JHN), the
CRD of the rat cargo-transporting lectin ERGIC-
53 (p58/MR60) (c; 1R1Z), one subunit of the
human pentraxin serum amyloid P component
in complex with MO
β
DG (d; 1GYK), the fi fth
laminin G-like module of the mouse laminin
α
2
-
chain (e; 1QU0), human annexin A2 starting at
Asn31 in complex with a heparin tetrasaccha-
ride (f; 2HYU; for details of heparin structure
and conformations of IdoA, please see Figures
1.6 and 1.7 d), the fucose - specifi c agglutinin
from the European eel
(Anguilla anguilla)
(g;
1K12), the construct of CRD/epidermal-growth-
factor-like domain of human C-type lectin P-
selectin in complex with sialyl Le
x
tetrasaccha-
ride (CD62P) (h; 1G1R), the CRD of human
C - type lectin dendritic - cell - specifi c ICAM - 3 -
grabbing non - integrin (DC - SIGN, CD209) in
complex with the pentasaccharide lacto-
N -
fuco-
pentaose III (i; 1SL5), soluble extracytoplasmic
domain (Asn81/STOP155) of the bovine cation-
dependent mannose - 6 - phosphate receptor in
complex with pentamannosyl phosphate (j;
1C39), the
Pseudomonas aeruginosa
lectin I (PA-
IL) in complex with galactose (k; 1OKO) and the
Pseudomonas aeruginosa
lectin II in complex
with fucose (PA-IIL) (l; 1GZT). Processing of
PDB entries kindly provided by H.-C. Siebert.
