| Full text | |
| Author(s): |
dos Santos Cabrera, Marcia Perez
[1, 2]
;
Baldissera, Gisele
[1, 3]
;
Silva-Goncalves, Laiz da Costa
[4]
;
de Souza, Bibiana Monson
[5]
;
Riske, Karin A.
[4]
;
Palma, Mario Sergio
[5]
;
Ruggiero, Jose Roberto
[1]
;
Arcisio-Miranda, Manoel
[4]
Total Authors: 8
|
| Affiliation: | [1] Univ Estadual Paulista, Dept Fis, BR-15054000 Sao Paulo - Brazil
[2] Univ Estadual Paulista, Dept Quim & Ciencias Ambientais, BR-15054000 Sao Paulo - Brazil
[3] Fac Tecnol Catanduva, BR-15800200 Sao Paulo - Brazil
[4] Univ Fed Sao Paulo, Dept Biofis, BR-04023062 Sao Paulo - Brazil
[5] Univ Estadual Paulista, Ctr Estudos Insetos Sociais, BR-13506900 Sao Paulo - Brazil
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | BIOCHEMISTRY; v. 53, n. 29, p. 4857-4868, JUL 29 2014. |
| Web of Science Citations: | 8 |
| Abstract | |
Jelleines are four naturally occurring peptides that comprise approximately eight or nine C-terminal residues in the sequence of the major royal jelly protein 1 precursor (Apis mellifera). The difference between these peptides is limited to one residue in the sequence, but this residue has a significant impact in their efficacy as antimicrobials. In peptidebilayer experiments, we demonstrated that the lytic, poreforming activity of Jelleine-I is similar to that of other cationic antimicrobial peptides, which exhibit stronger activity on anionic bilayers. Results from molecular dynamics simulations suggested that the presence of a proline residue at the first position is the underlying reason for the higher efficacy of Jelleine-I compared with the other jelleines. Additionally, simulations suggested that Jelleine-I tends to form aggregates in water and in the presence of mimetic membrane environments. Combined experimental evidence and simulations showed that the protonation of the histidine residue potentiates the interaction with anionic palmitoyloleoyl-phosphatidylcholine/palmitoyl-oleoyl-phosphatidylglycero l (POPC/POPG) (70:30) bilayers and reduces the free energy barrier for water passage. The interaction is driven by electrostatic interactions with the headgroup region of the bilayer with some disturbance of the acyl chain region. Our findings point to a mechanism of action by which aggregated Jelleine-I accumulates on the headgroup region of the membrane. Remaining in this form, Jelleine-I could exert pressure to accommodate its polar and nonpolar residues on the amphiphilic environment of the membrane. This pressure could open pores or defects, could disturb the bilayer continuity, and leakage would be observed. The agreement between experimental data and simulations in mimetic membranes suggests that this approach may be a valuable tool to the understanding of the molecular mechanisms of action. (AU) | |
| FAPESP's process: | 06/57122-7 - Procura de compostos lideres para o desenvolvimento racional de novos farmacos e pesticidas a partir bioprospeccao da fauna de artropodes brasileiros. |
| Grantee: | Mario Sergio Palma |
| Support Opportunities: | BIOTA-FAPESP Program - Thematic Grants |
| FAPESP's process: | 10/11823-0 - Mechanisms of interactions of lipid bilayers and amphiphilic substances of therapeutic interest |
| Grantee: | Marcia Perez dos Santos Cabrera |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 10/52077-9 - Aspectos moleculares do sensor de voltagem de canais ionicos:estrutura cinetica e evolucao. |
| Grantee: | Manoel de Arcisio Miranda Filho |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 12/24259-0 - Peptide and chitosan conjugates with pharmacological potential: synthesis, prospecting of activity in membrane mimetic systems, and evaluation in cells |
| Grantee: | Marcia Perez dos Santos Cabrera |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 11/51684-1 - Biologia de sistemas como estrategia experimental para a descoberta de novos produtos naturais na fauna de artropodes peconhentos do estado de sao paulo. |
| Grantee: | Mario Sergio Palma |
| Support Opportunities: | BIOTA-FAPESP Program - Thematic Grants |