1U4M

human RANTES complexed to heparin-derived disaccharide III-S

Summary for 1U4M

• Entry DOI: 10.2210/pdb1u4m/pdb
• Related: 1b3a 1eqt 1hrj 1rtn 1rto 1u4l 1u4p 1u4r
• Related PRD ID: PRD_900094
• Descriptor: Small inducible cytokine A5, 4-deoxy-2-O-sulfo-alpha-L-threo-hex-4-enopyranuronic acid-(1-4)-2-deoxy-2-(sulfoamino)-alpha-D-glucopyranose, ACETIC ACID, ... (4 entities in total)
• Functional Keywords: chemoattractant, cytokine, chemokine, rantes, glycosaminoglycan, protein-heparin disaccharide complex, attractant
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 16281.48

Authors

Shaw, J.P.,Johnson, Z.,Borlat, F.,Zwahlen, C.,Kungl, A.,Roulin, K.,Harrenga, A.,Wells, T.N.C.,Proudfoot, A.E.I. (deposition date: 2004-07-26, release date: 2004-11-09, Last modification date: 2024-11-13)

Primary citation

Shaw, J.P.,Johnson, Z.,Borlat, F.,Zwahlen, C.,Kungl, A.,Roulin, K.,Harrenga, A.,Wells, T.N.,Proudfoot, A.E.
The X-ray structure of RANTES: heparin-derived disaccharides allows the rational design of chemokine inhibitors.
Structure, 12:2081-2093, 2004

PubMed Abstract: 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.

PubMed: 15530372
DOI: 10.1016/j.str.2004.08.014

Experimental method

X-RAY DIFFRACTION (2 Å)