1u4l
From Proteopedia
(New page: 200px<br /> <applet load="1u4l" size="450" color="white" frame="true" align="right" spinBox="true" caption="1u4l, resolution 2.00Å" /> '''human RANTES comple...) |
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| - | [[Image:1u4l.gif|left|200px]]<br /> | + | [[Image:1u4l.gif|left|200px]]<br /><applet load="1u4l" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1u4l" size=" | + | |
caption="1u4l, resolution 2.00Å" /> | caption="1u4l, resolution 2.00Å" /> | ||
'''human RANTES complexed to heparin-derived disaccharide I-S'''<br /> | '''human RANTES complexed to heparin-derived disaccharide I-S'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The biological activity of chemokines requires interactions with cell | + | The biological activity of chemokines requires interactions with cell surface proteoglycans. We have determined the structure of the chemokine RANTES (regulated on activation normal T cell expressed) in the presence of heparin-derived disaccharide analogs by X-ray crystallography. These structures confirm the essential role of the BBXB motif in the interaction between the chemokine and the disaccharide. Unexpected interactions were observed in the 30s loop and at the amino terminus. Mutant RANTES molecules were designed to abrogate these interactions and their biological activity examined in vivo. The K45E mutant within the BBXB motif lost the capacity to bind heparin and the ability to elicit cellular recruitment. The Y3A mutant maintained its capacity to bind heparin but was unable to elicit cellular recruitment. Finally, a tetrasaccharide is the smallest oligosaccharide which effectively abolishes the ability of RANTES to recruit cells in vivo. These crystallographic structures provide a description of the molecular interaction of a chemokine with glycosaminoglycans. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1U4L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with H1S and ACY as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1U4L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=H1S:'>H1S</scene> and <scene name='pdbligand=ACY:'>ACY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U4L OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Johnson, Z.]] | [[Category: Johnson, Z.]] | ||
[[Category: Kungl, A.]] | [[Category: Kungl, A.]] | ||
| - | [[Category: Proudfoot, A | + | [[Category: Proudfoot, A E.I.]] |
[[Category: Roulin, K.]] | [[Category: Roulin, K.]] | ||
| - | [[Category: Shaw, J | + | [[Category: Shaw, J P.]] |
| - | [[Category: Wells, T | + | [[Category: Wells, T N.C.]] |
[[Category: Zwahlen, C.]] | [[Category: Zwahlen, C.]] | ||
[[Category: ACY]] | [[Category: ACY]] | ||
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[[Category: rantes]] | [[Category: rantes]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:20:33 2008'' |
Revision as of 13:20, 21 February 2008
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human RANTES complexed to heparin-derived disaccharide I-S
Contents |
Overview
The biological activity of chemokines requires interactions with cell surface proteoglycans. We have determined the structure of the chemokine RANTES (regulated on activation normal T cell expressed) in the presence of heparin-derived disaccharide analogs by X-ray crystallography. These structures confirm the essential role of the BBXB motif in the interaction between the chemokine and the disaccharide. Unexpected interactions were observed in the 30s loop and at the amino terminus. Mutant RANTES molecules were designed to abrogate these interactions and their biological activity examined in vivo. The K45E mutant within the BBXB motif lost the capacity to bind heparin and the ability to elicit cellular recruitment. The Y3A mutant maintained its capacity to bind heparin but was unable to elicit cellular recruitment. Finally, a tetrasaccharide is the smallest oligosaccharide which effectively abolishes the ability of RANTES to recruit cells in vivo. These crystallographic structures provide a description of the molecular interaction of a chemokine with glycosaminoglycans.
Disease
Known diseases associated with this structure: HIV-1 disease, delayed progression of OMIM:[187011], HIV-1 disease, rapid progression of OMIM:[187011]
About this Structure
1U4L is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
The X-ray structure of RANTES: heparin-derived disaccharides allows the rational design of chemokine inhibitors., Shaw JP, Johnson Z, Borlat F, Zwahlen C, Kungl A, Roulin K, Harrenga A, Wells TN, Proudfoot AE, Structure. 2004 Nov;12(11):2081-93. PMID:15530372
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