 |
PDBsum entry 2kv3
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Sugar binding protein
|
PDB id
|
|
|
|
2kv3
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Human regiv protein adopts a typical c-Type lectin fold but binds mannan with two calcium-Independent sites.
|
|
|
Authors
|
|
M.R.Ho,
Y.C.Lou,
S.Y.Wei,
S.C.Luo,
W.C.Lin,
P.C.Lyu,
C.Chen.
|
|
|
Ref.
|
|
J Mol Biol, 2010,
402,
682-695.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Human RegIV protein, which contains a sequence motif homologous to
calcium-dependent (C-type) lectin-like domain, is highly expressed in mucosa
cells of the gastrointestinal tract during pathogen infection and carcinogenesis
and may be applied in both diagnosis and treatment of gastric and colon cancers.
Here, we provide evidence that, unlike other C-type lectins, human RegIV binds
to polysaccharides, mannan, and heparin in the absence of calcium. To elucidate
the structural basis for carbohydrate recognition by NMR, we generated the
mutant with Pro91 replaced by Ser (hRegIV-P91S) and showed that the structural
property and carbohydrate binding ability of hRegIV-P91S are almost identical
with those of wild-type protein. The solution structure of hRegIV-P91S was
determined, showing that it adopts a typical fold of C-type lectin. Based on the
chemical shift perturbations of amide resonances, two calcium-independent
mannan-binding sites were proposed. One site is similar to the
calcium-independent sugar-binding site on human RegIII and Langerin.
Interestingly, the other site is adjacent to the conserved calcium-dependent
site at position Ca-2 of typical C-type lectins. Moreover, model-free analysis
of (15)N relaxation parameters and simplified Carr-Purcell-Meiboom-Gill
relaxation dispersion experiments showed that a slow microsecond-to-millisecond
time-scale backbone motion is involved in mannan binding by this site,
suggesting a potential role for specific carbohydrate recognition. Our findings
shed light on the sugar-binding mode of Reg family proteins, and we postulate
that Reg family proteins evolved to bind sugar without calcium to keep the
carbohydrate recognition activity under low-pH environments in the
gastrointestinal tract.
|
|
|
|
|
|
|
