2N0X
Three dimensional structure of EPI-X4, a human albumin-derived peptide that regulates innate immunity through the CXCR4/CXCL12 chemotactic axis and antagonizes HIV-1 entry
Summary for 2N0X
| Entry DOI | 10.2210/pdb2n0x/pdb |
| NMR Information | BMRB: 25539 |
| Descriptor | Serum albumin (1 entity in total) |
| Functional Keywords | antagonist, inhibitor peptide, peptide binding protein |
| Biological source | Homo sapiens (human) |
| Cellular location | Secreted: P02768 |
| Total number of polymer chains | 1 |
| Total formula weight | 1833.20 |
| Authors | Perez-Castells, J.,Canales, A.,Jimenez-Barbero, J.,Gimenez-Gallego, G. (deposition date: 2015-03-18, release date: 2015-04-29, Last modification date: 2024-05-15) |
| Primary citation | Zirafi, O.,Kim, K.A.,Standker, L.,Mohr, K.B.,Sauter, D.,Heigele, A.,Kluge, S.F.,Wiercinska, E.,Chudziak, D.,Richter, R.,Moepps, B.,Gierschik, P.,Vas, V.,Geiger, H.,Lamla, M.,Weil, T.,Burster, T.,Zgraja, A.,Daubeuf, F.,Frossard, N.,Hachet-Haas, M.,Heunisch, F.,Reichetzeder, C.,Galzi, J.L.,Perez-Castells, J.,Canales-Mayordomo, A.,Jimenez-Barbero, J.,Gimenez-Gallego, G.,Schneider, M.,Shorter, J.,Telenti, A.,Hocher, B.,Forssmann, W.G.,Bonig, H.,Kirchhoff, F.,Munch, J. Discovery and characterization of an endogenous CXCR4 antagonist. Cell Rep, 11:737-747, 2015 Cited by PubMed Abstract: CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation. PubMed: 25921529DOI: 10.1016/j.celrep.2015.03.061 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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