2K03
Structure of SDF1 in complex with the CXCR4 N-terminus containing a sulfotyrosine at postition 21
Summary for 2K03
| Entry DOI | 10.2210/pdb2k03/pdb |
| Related | 2K01 2K04 2K05 |
| NMR Information | BMRB: 15635 |
| Descriptor | Stromal cell-derived factor 1, C-X-C chemokine receptor type 4 (2 entities in total) |
| Functional Keywords | stromal cell derived factor-1, sdf1-alpha, cxcl12, cxcr4, chemokine, sulfotyrosine, locked dimer, alternative splicing, chemotaxis, cytokine, growth factor, secreted, g-protein coupled receptor, glycoprotein, host-virus interaction, membrane, receptor, sulfation, transducer, transmembrane |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 25575.19 |
| Authors | Volkman, B.F.,Veldkamp, C.T.,Peterson, F.C. (deposition date: 2008-01-24, release date: 2008-10-28, Last modification date: 2024-10-09) |
| Primary citation | Veldkamp, C.T.,Seibert, C.,Peterson, F.C.,De la Cruz, N.B.,Haugner, J.C.,Basnet, H.,Sakmar, T.P.,Volkman, B.F. Structural basis of CXCR4 sulfotyrosine recognition by the chemokine SDF-1/CXCL12 Sci.Signal., 1:ra4-ra4, 2008 Cited by PubMed Abstract: Stem cell homing and breast cancer metastasis are orchestrated by the chemokine stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4. Here, we report the nuclear magnetic resonance structure of a constitutively dimeric SDF-1 in complex with a CXCR4 fragment that contains three sulfotyrosine residues important for a high-affinity ligand-receptor interaction. CXCR4 bridged the SDF-1 dimer interface so that sulfotyrosines sTyr7 and sTyr12 of CXCR4 occupied positively charged clefts on opposing chemokine subunits. Dimeric SDF-1 induced intracellular Ca2+ mobilization but had no chemotactic activity; instead, it prevented native SDF-1-induced chemotaxis, suggesting that it acted as a potent partial agonist. Our work elucidates the structural basis for sulfotyrosine recognition in the chemokine-receptor interaction and suggests a strategy for CXCR4-targeted drug development. PubMed: 18799424DOI: 10.1126/scisignal.1160755 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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