1FWU

CRYSTAL STRUCTURE OF THE CYSTEINE-RICH DOMAIN OF MANNOSE RECEPTOR COMPLEXED WITH 3-SO4-LEWIS(X)

Summary for 1FWU

• Entry DOI: 10.2210/pdb1fwu/pdb
• Related: 1dqg
• Descriptor: CYSTEINE-RICH DOMAIN OF MANNOSE RECEPTOR, alpha-L-fucopyranose-(1-3)-[3-O-sulfo-beta-D-galactopyranose-(1-4)]methyl 2-acetamido-2-deoxy-beta-D-glucopyranoside (3 entities in total)
• Functional Keywords: beta trefoil, mannose receptor, sulfated carbohydrate, sugar binding protein
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 1
• Total formula weight: 16068.91

Authors

Liu, Y.,Misulovin, Z.,Bjorkman, P.J. (deposition date: 2000-09-24, release date: 2001-01-17, Last modification date: 2024-10-16)

Primary citation

Liu, Y.,Misulovin, Z.,Bjorkman, P.J.
The molecular mechanism of sulfated carbohydrate recognition by the cysteine-rich domain of mannose receptor.
J.Mol.Biol., 305:481-490, 2001

PubMed 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.

PubMed: 11152606
DOI: 10.1006/jmbi.2000.4326

Experimental method

X-RAY DIFFRACTION (1.9 Å)