PDBsum entry 2kv3

Sugar binding protein

PDB id: 2kv3

Contents

Protein chain

131 a.a. *

* Residue conservation analysis

PDB id:

2kv3

Name:

Sugar binding protein

Title:

Human regenerating gene type iv (reg iv) protein, p91s mutant

Structure:

Regenerating islet-derived protein 4. Chain: a. Fragment: unp residues 28-158. Synonym: regenerating gene type iv, reg-4, regenerating islet-derived protein iv, reg iv, reg-like protein, gastrointestinal secretory protein. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: reg4. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

M.Ho,Y.Lou,C.Chen

Key ref:

M.R.Ho et al. (2010). Human RegIV protein adopts a typical C-type lectin fold but binds mannan with two calcium-independent sites. J Mol Biol, 402, 682-695. PubMed id: 20692269 DOI: 10.1016/j.jmb.2010.07.061

Date:

04-Mar-10 Release date: 18-Aug-10

Protein chain

Q9BYZ8  (REG4_HUMAN) -  Regenerating islet-derived protein 4 from Homo sapiens

Seq: 158 a.a.

Struc: 131 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/j.jmb.2010.07.061

J Mol Biol 402:682-695 (2010)

PubMed id: 20692269

Human RegIV protein adopts a typical C-type lectin fold but binds mannan with two calcium-independent sites.

M.R.Ho, Y.C.Lou, S.Y.Wei, S.C.Luo, W.C.Lin, P.C.Lyu, C.Chen.

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.