1u4l
From Proteopedia
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|PDB= 1u4l |SIZE=350|CAPTION= <scene name='initialview01'>1u4l</scene>, resolution 2.00Å | |PDB= 1u4l |SIZE=350|CAPTION= <scene name='initialview01'>1u4l</scene>, resolution 2.00Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=H1S:HEPARIN+DISACCHARIDE+I-S'>H1S</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= CCL5, SCYA5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= CCL5, SCYA5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1hrj|1HRJ]], [[1rtn|1RTN]], [[1rto|1RTO]], [[1b3a|1B3A]], [[1eqt|1EQT]], [[1u4r|1U4R]], [[1u4m|1U4M]], [[1u4p|1U4P]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1u4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u4l OCA], [http://www.ebi.ac.uk/pdbsum/1u4l PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1u4l RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: HIV-1 disease, delayed progression of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=187011 187011]], HIV-1 disease, rapid progression of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=187011 187011]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Wells, T N.C.]] | [[Category: Wells, T N.C.]] | ||
[[Category: Zwahlen, C.]] | [[Category: Zwahlen, C.]] | ||
| - | [[Category: ACY]] | ||
| - | [[Category: H1S]] | ||
[[Category: chemoattractant]] | [[Category: chemoattractant]] | ||
[[Category: chemokine]] | [[Category: chemokine]] | ||
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[[Category: rante]] | [[Category: rante]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:05:22 2008'' |
Revision as of 21:05, 30 March 2008
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| , resolution 2.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | CCL5, SCYA5 (Homo sapiens) | ||||||
| Related: | 1HRJ, 1RTN, 1RTO, 1B3A, 1EQT, 1U4R, 1U4M, 1U4P
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
human RANTES complexed to heparin-derived disaccharide I-S
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.
About this Structure
1U4L is a Single protein structure of sequence from Homo sapiens. 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
Page seeded by OCA on Mon Mar 31 00:05:22 2008
