PDBsum entry: 1fwu

Sugar binding protein

PDB id: 1fwu

Contents

Protein chain

134 a.a. *

Ligands

SGA-MAG-FUC

Waters ×130

* Residue conservation analysis

PDB id:

1fwu

Name:

Sugar binding protein

Title:

Crystal structure of the cysteine-rich domain of mannose receptor complexed with 3-so4-lewis(x)

Structure:

Cysteine-rich domain of mannose receptor. Chain: a. Fragment: n-terminal domain of mannose receptor. Engineered: yes. Other_details: complexed with 3-so4-lewis(x)

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: sus scrofa. Expression_system_taxid: 9823. Expression_system_cell: 293 cells

Resolution:

1.90Å R-factor: 0.213 R-free: 0.237

Authors:

Y.Liu,Z.Misulovin,P.J.Bjorkman

Key ref:

Y.Liu et al. (2001). The molecular mechanism of sulfated carbohydrate recognition by the cysteine-rich domain of mannose receptor. J Mol Biol, 305, 481-490. PubMed id: 11152606 DOI: 10.1006/jmbi.2000.4326

Date:

24-Sep-00 Release date: 17-Jan-01

Protein chain

Q61830  (MRC1_MOUSE) -  Macrophage mannose receptor 1

Seq: 1456 a.a.

Struc: 134 a.a.

DOI no: 10.1006/jmbi.2000.4326

J Mol Biol 305:481-490 (2001)

PubMed id: 11152606

The molecular mechanism of sulfated carbohydrate recognition by the cysteine-rich domain of mannose receptor.

Y.Liu, Z.Misulovin, P.J.Bjorkman.

ABSTRACT

The mannose receptor (MR) binds foreign and host ligands through interactions with their carbohydrates. Two portions of MR have distinct carbohydrate recognition properties. One is conferred by the amino-terminal cysteine-rich domain (Cys-MR), which plays a critical role in binding sulfated glycoproteins including pituitary hormones. The other is achieved by tandemly arranged C-type lectin domains that facilitate carbohydrate-dependent uptake of infectious microorganisms. This dual carbohydrate binding specificity enables MR to bind ligands by interacting with both sulfated and non-sulfated polysaccharide chains. We previously determined crystal structures of Cys-MR complexed with 4-SO(4)-N-acetylglucosamine and with an unidentified ligand resembling Hepes (N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid]). In continued efforts to elucidate the mechanism of sulfated carbohydrate recognition by Cys-MR, we characterized the binding affinities between Cys-MR and potential carbohydrate ligands using a fluorescence-based assay. We find that Cys-MR binds sulfated carbohydrates with relatively high affinities (K(D)=0.1 mM to 1.0 mM) compared to the affinities of other lectins. Cys-MR also binds Hepes with a K(D) value of 3.9 mM, consistent with the suggestion that the ligand in the original Cys-MR crystal structure is Hepes. We also determined crystal structures of Cys-MR complexed with 3-SO(4)-Lewis(x), 3-SO(4)-Lewis(a), and 6-SO(4)-N-acetylglucosamine at 1.9 A, 2.2 A, and 2.5 A resolution, respectively, and the 2.0 A structure of Cys-MR that had been treated to remove Hepes. The conformation of the Cys-MR binding site is virtually identical in all Cys-MR crystal structures, suggesting that Cys-MR does not undergo conformational changes upon ligand binding. The structures are used to rationalize the binding affinities derived from the biochemical studies and to elucidate the molecular mechanism of sulfated carbohydrate recognition by Cys-MR.

Selected figure(s)

Figure 1.
Figure 1. Structure of Cys-MR bound to 4-SO[4]-GalNAc. Ribbon diagram of the Cys-MR structure with lobes I, II, and III indicated in different colors. Disulfide bonds are yellow and 4-SO[4]-GalNAc is shown in ball-and-stick representation. Trp117 is highlighted in blue.

Figure 5.
Figure 5. Comparson of Cys-MR binding to 3-SO[4]-Gal and 4-SO[4]-GalNAc. Stereo view of the interactions between Cys-MR and the 3-SO[4]-Gal portion of 3-SO[4]-Lewisx and 4-SO[4]-GalNAc. Hydrogen bonds between ligand and protein atoms are indicated by dotted green lines.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 305, 481-490) copyright 2001.

Figures were selected by an automated process.