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Crystal Structure of the Cysteine-Rich Domain of Mannose Receptor Complexed with a Sulfated Carbohydrate Ligand

Liu, By Yang and Chirino, Arthur J. and Misulovin, Ziva and Leteux, Christine and Feizi, Ten and Nussenzweig, Michel C. and Bjorkman, Pamela J. (2000) Crystal Structure of the Cysteine-Rich Domain of Mannose Receptor Complexed with a Sulfated Carbohydrate Ligand. Journal of Experimental Medicine, 191 (7). pp. 1105-1115. ISSN 0022-1007. http://resolver.caltech.edu/CaltechAUTHORS:20111129-160812983

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Abstract

The macrophage and epithelial cell mannose receptor (MR) binds carbohydrates on foreign and host molecules. Two portions of MR recognize carbohydrates: tandemly arranged C-type lectin domains facilitate carbohydrate-dependent macrophage uptake of infectious organisms, and the NH2-terminal cysteine-rich domain (Cys-MR) binds to sulfated glycoproteins including pituitary hormones. To elucidate the mechanism of sulfated carbohydrate recognition, we determined crystal structures of Cys-MR alone and complexed with 4-sulfated-N-acetylgalactosamine at 1.7 and 2.2 Å resolution, respectively. Cys-MR folds into an approximately three-fold symmetric β-trefoil shape resembling fibroblast growth factor. The sulfate portions of 4-sulfated-N-acetylgalactosamine and an unidentified ligand found in the native crystals bind in a neutral pocket in the third lobe. We use the structures to rationalize the carbohydrate binding specificities of Cys-MR and compare the recognition properties of Cys-MR with other β-trefoil proteins.


Item Type:Article
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URLURL TypeDescription
http://dx.doi.org/10.1084/jem.191.7.1105 DOIUNSPECIFIED
http://jem.rupress.org/content/191/7/1105PublisherUNSPECIFIED
Additional Information:© 2000 The Rockefeller University Press. Submitted: 7 December 1999; Revised: 27 January 2000; Accepted: 4 February 2000. We thank S. Gordon and L. Martínez-Pomares for the Cys-MR-Fc expression vector, G. Hathaway and the California Institute of Technology’s Protein/Peptide Micro Analytical Laboratory for peptide analyses, M.J. Bennett, A.P. Yeh, L.M. Sanchez, H.J. Chiu, S. Ding, and M. Williamson for crystallographic assistance, and W.I. Weis, M.E. Taylor, and members of the Bjorkman laboratory for critical reading of the manuscript. Coordinates have been submitted to the Protein Data Bank (available at www.rcsb.org/pdb/ under accession nos. IDQG and IDQO). This work was supported by the Howard Hughes Medical Institute (P.J. Bjorkman and M.C. Nussenzweig) and grants from the National Institutes of Health (M.C. Nussenzweig). Y. Liu was a recipient of Ferguson Fund predoctoral Fellowship and Teaching Assistantship (California Institute of Technology).
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Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NIHUNSPECIFIED
Subject Keywords:β-trefoil protein; hydrogen bond network; multilectin receptor; pituitary hormones; sulfated GalNAc
Record Number:CaltechAUTHORS:20111129-160812983
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20111129-160812983
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:28237
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:29 Feb 2012 00:06
Last Modified:26 Dec 2012 14:33

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