Dual structural requirements for multilineage hematopoietic-suppressive activity of chemokine-derived peptides
| Autor: | Noureddine Lazar, M. Delepierre, Z. C. Han, Mohamed Rholam, L. Lecomte-Raclet, M. Alemany, J. P. Caen, Paul Cohen, C. Simenel |
|---|---|
| Přispěvatelé: | Institut des vaisseaux et du sang, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité mixte de recherche 7631 CNRS, Université Pierre et Marie Curie - Paris 6 (UPMC), Biologie structurale et agents infectieux (BSAI), Institut Pasteur [Paris], Key Laboratory of Hematology, Institute of hematology, Institut Pasteur [Paris] (IP) |
| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
Chemokine
Protein Conformation Amino Acid Motifs MESH: Hematopoiesis MESH: Protein Structure Secondary Peptide MESH: Amino Acid Sequence Platelet Factor 4 Biochemistry Protein Structure Secondary MESH: Circular Dichroism Mice MESH: Amino Acid Motifs 0302 clinical medicine MESH: Protein Conformation MESH: Structure-Activity Relationship MESH: Platelet Factor 4 Spectroscopy Fourier Transform Infrared MESH: Nuclear Magnetic Resonance Biomolecular MESH: Animals Receptor MESH: Peptide Fragments chemistry.chemical_classification 0303 health sciences Mice Inbred BALB C biology [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] Circular Dichroism Biological activity MESH: Chemokines Growth Inhibitors Haematopoiesis Chemokines Molecular Sequence Data MESH: Mice Inbred BALB C MESH: Spectroscopy Fourier Transform Infrared 03 medical and health sciences Structure-Activity Relationship In vivo Animals Cell Lineage Amino Acid Sequence Nuclear Magnetic Resonance Biomolecular MESH: Mice 030304 developmental biology MESH: Molecular Sequence Data MESH: Cell Lineage In vitro Peptide Fragments Hematopoiesis MESH: Growth Inhibitors chemistry biology.protein Platelet factor 4 030215 immunology |
| Zdroj: | Biochemistry Biochemistry, American Chemical Society, 2000, 39 (31), pp.9612-22. ⟨10.1021/bi0004100⟩ Biochemistry, 2000, 39 (31), pp.9612-22. ⟨10.1021/bi0004100⟩ |
| ISSN: | 0006-2960 1520-4995 |
| DOI: | 10.1021/bi0004100⟩ |
| Popis: | International audience; Many chemokines have direct suppressive activity in vitro and in vivo on primitive hematopoietic cells. However, few chemokine-derived peptides have shown a significant activity in inhibiting hematopoiesis. Interestingly, a peptide derived from the 34-58 sequence of the CXC chemokine platelet factor 4 (PF4) produced a 30-40% inhibition of proliferation of murine hematopoietic progenitors (CFU-MK, CFU-GM, and BFU-E) in vitro, at concentrations of 30-60-fold lower than PF4. The aim of the present work was to define the structural parameters and motifs involved in conferring biological activity to the peptide PF4(34-58). Both structural predictions and determinations revealed a new helical motif that was further localized between residues 38 and 46. This helix was necessary for binding of the peptide and for permitting the functional DLQ motif at position 54-56 to activate the putative receptor site. Peptides lacking either the helical or the DLQ motif were devoid of inhibitory activity on the hematopoietic progenitors in vitro. However, among inactive peptides, only those having the helical motif counteracted the inhibition induced by the active peptide PF4(34-58). This suggested that the helix might be required for peptide interactions with a putative receptor site, whereas the DLQ motif would be implicated in the activation of this receptor. These results identify for the first time the dual requirements for the design of chemokine-derived peptides with high suppressive activity on hematopoiesis, as well as for the design of molecules with antagonistic action. |
| Databáze: | OpenAIRE |
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