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

Liu, Yang and Misulovin, Ziva and Bjorkman, Pamela J. (2001) The molecular mechanism of sulfated carbohydrate recognition by the cysteine-rich domain of mannose receptor. Journal of Molecular Biology, 305 (3). pp. 481-490. ISSN 0022-2836. https://resolver.caltech.edu/CaltechAUTHORS:20170327-125328321

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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 Å, 2.2 Å, and 2.5 Å resolution, respectively, and the 2.0 Å 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1006/jmbi.2000.4326DOIArticle
http://www.sciencedirect.com/science/article/pii/S0022283600943262PublisherArticle
ORCID:
AuthorORCID
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 2001 Academic Press. Received 20 August 2000, Revised 1 November 2000, Accepted 6 November 2000. We thank Ten Feizi, Christine Leteux, Heide Kogelberg, and members of the Bjorkman laboratory for critical reading of the manuscript, and Michel Nussenzweig for contributions to earlier phases of the project. Data bank accession numbers: Coordinates have been deposited in the RCSB Protein Data Bank under accession codes 1FWV (3-SO4-Lewisa complex) and 1FWU (3-SO4-Lewisx complex).
Subject Keywords:β-trefoil protein; fluorescence spectrophotometery; mannose receptor; pituitary hormones; sulfated carbohydrates
Issue or Number:3
Record Number:CaltechAUTHORS:20170327-125328321
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170327-125328321
Official Citation:Yang Liu, Ziva Misulovin, Pamela J. Bjorkman, The molecular mechanism of sulfated carbohydrate recognition by the cysteine-rich domain of mannose receptor1, Journal of Molecular Biology, Volume 305, Issue 3, 19 January 2001, Pages 481-490, ISSN 0022-2836, http://dx.doi.org/10.1006/jmbi.2000.4326. (http://www.sciencedirect.com/science/article/pii/S0022283600943262)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75420
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:27 Mar 2017 20:03
Last Modified:03 Oct 2019 16:50

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