1fwu: Difference between revisions

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

OverviewOverview

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.

About this StructureAbout this Structure

1FWU is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

ReferenceReference

The molecular mechanism of sulfated carbohydrate recognition by the cysteine-rich domain of mannose receptor., Liu Y, Misulovin Z, Bjorkman PJ, J Mol Biol. 2001 Jan 19;305(3):481-90. PMID:11152606

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-[[Image:1fwu.gif|left|200px]]<br /><applet load="1fwu" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1fwu.gif|left|200px]]<br /><applet load="1fwu" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1fwu, resolution 1.9&Aring;" />
 '''CRYSTAL STRUCTURE OF THE CYSTEINE-RICH DOMAIN OF MANNOSE RECEPTOR COMPLEXED WITH 3-SO4-LEWIS(X)'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-FWU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FWU OCA].
+FWU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FWU OCA].
 ==Reference==
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 [[Category: Mus musculus]]
 [[Category: Single protein]]
-[[Category: Bjorkman, P.J.]]
+[[Category: Bjorkman, P J.]]
 [[Category: Liu, Y.]]
 [[Category: Misulovin, Z.]]
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 [[Category: sulfated carbohydrate]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 15:23:59 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:43:28 2008''