title: Folding propensity and biological activity of peptides: New insights from conformational properties of a novel peptide derived from Vitreoscilla haemoglobin.
abstract: The synthetic peptide Vitr-p-13 (YPIVGQELLGAIK-NH(2)), derived from the bacterial dimeric Vitreoscilla haemoglobin (VHb) in the position 95-107, is characterized by a pre-eminent "statistical coil" conformation in water as demonstrated by CD experiments and long time-scale MD simulations. In particular, Vitr-p-13 does not spontaneously adopt an alpha-helix folding in water, but it is rather preferentially found in beta-hairpin-like conformations. Long time-scale MD simulations have also shown that Vitr-p-13 displays a "topological-trigger" which initiates alpha-helix folding within residues 7-10, exactly like seen in the temporins, a group of linear, membrane-active antimicrobial peptides of similar length. At variance with temporins, in Vitr-p-13 such a process is energetically very demanding (+10 kJ/mol) in water at 300 K, and the peptide was found to be unable to bind model membranes in vitro and was devoid of antimicrobial activity. The present results, compared with previous studies on similar systems, strengthen the hypothesis of the requirement of a partial folding when still in aqueous environment to allow a peptide to interact with cell-membranes and eventually exert membrane perturbation-related antibiotic effects on target microbial cells.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biomediche, Università de L'Aquila, Italia.
authors.forename: A
authors.initials: A
authors.lastname: Bozzi
authors.forename: C
authors.initials: C
authors.lastname: Coccia
authors.forename: A
authors.initials: A
authors.lastname: Di Giulio
authors.forename: A C
authors.initials: AC
authors.lastname: Rinaldi
authors.forename: A
authors.initials: A
authors.lastname: Amadei
authors.forename: G
authors.initials: G
authors.lastname: Mignogna
authors.forename: A
authors.initials: A
authors.lastname: Bonamore
authors.forename: A
authors.initials: A
authors.lastname: Fais
authors.forename: M
authors.initials: M
authors.lastname: Aschi
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D054793:Truncated Hemoglobins; D020589:Vitreoscilla / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D006454:Hemoglobins; D010455:Peptides; D054793:Truncated Hemoglobins; C082613:hemoglobin protein, Vitreoscilla