title: New insights into the molecular interaction of the C-terminal sequence of CXCL4 with fibroblast growth factor-2.
abstract: Full-length CXCL4 chemokine and a peptide derived from its carboxyl-terminal domain exhibits significant antiangiogenic and anti-tumor activity in vivo and in vitro by interacting with fibroblast growth factor (FGF). In this study we used NMR spectroscopy to characterize at a molecular level the interactions between CXCL4 (47-70) and FGF-2 identifying the peptide residues mainly involved in the contact area with the growth factor. Altogether NMR data point to a major role of the hydrophobic contributions of the C-terminal region of CXCL4 (47-70) peptide in addition to specific contacts established by the N-terminal region through cysteine side chain. The proposed recognition mode constitutes a rationale for the observed effects of CXCL4 (47-70) on FGF-2 biological activity and lays the basis for developing novel inhibitors of angiogenesis.
authors.affiliation: Istituto per lo Studio delle Macromolecole, Consiglio Nazionale delle Ricerche, Via Bassini 15, 20133 Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ragona
authors.forename: Simona
authors.initials: S
authors.lastname: Tomaselli
authors.forename: Cathy
authors.initials: C
authors.lastname: Quemener
authors.forename: Lucia
authors.initials: L
authors.lastname: Zetta
authors.forename: Andreas
authors.initials: A
authors.lastname: Bikfalvi
mesh_terms: D000595:Amino Acid Sequence; D003545:Cysteine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010978:Platelet Factor 4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary
chemical_list: D010455:Peptides; D016222:Fibroblast Growth Factor 2; D010978:Platelet Factor 4; D003545:Cysteine