Probing the Interaction of Brain Fatty Acid Binding Protein (B-FABP) with Model Membranes

Author(s)

Dyszy, Fabio ^[1] ; Pinto, Andressa P. A. ^[1] ; Araujo, Ana P. U. ^[1] ; Costa-Filho, Antonio J. ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Inst Fis Sao Carlos, Grp Biofis Mol Sergio Mascarenhas, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Fac Filosofia, Lab Biofis Mol, Dept Fis, Sao Paulo - Brazil

• Document type: Journal article
• Source: PLoS One; v. 8, n. 3 MAR 28 2013.
• Web of Science Citations: 6

Abstract

Brain fatty acid-binding protein (B-FABP) interacts with biological membranes and delivers polyunsaturated fatty acids (FAs) via a collisional mechanism. The binding of FAs in the protein and the interaction with membranes involve a motif called ``portal region'', formed by two small alpha-helices, A1 and A2, connected by a loop. We used a combination of site-directed mutagenesis and electron spin resonance to probe the changes in the protein and in the membrane model induced by their interaction. Spin labeled B-FABP mutants and lipidic spin probes incorporated into a membrane model confirmed that BFABP interacts with micelles through the portal region and led to structural changes in the protein as well in the micelles. These changes were greater in the presence of LPG when compared to the LPC models. ESR spectra of B-FABP labeled mutants showed the presence of two groups of residues that responded to the presence of micelles in opposite ways. In the presence of lysophospholipids, group I of residues, whose side chains point outwards from the contact region between the helices, had their mobility decreased in an environment of lower polarity when compared to the same residues in solution. The second group, composed by residues with side chains situated at the interface between the a-helices, experienced an increase in mobility in the presence of the model membranes. These modifications in the ESR spectra of B-FABP mutants are compatible with a less ordered structure of the portal region inner residues (group II) that is likely to facilitate the delivery of FAs to target membranes. On the other hand, residues in group I and micelle components have their mobilities decreased probably as a result of the formation of a collisional complex. Our results bring new insights for the understanding of the gating and delivery mechanisms of FABPs. (AU)

• FAPESP's process: 10/17662-8 - Electron magnetic resonance in studies of structure, function and interactions of biologically-relevant molecules
• Grantee: Antonio José da Costa Filho
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/15810-2 - Site-directed spin labeling and Electron Magnetic Resonance: A new approach in studies of lipid-protein and protein-protein interactions
• Grantee: Fábio Henrique Dyszy
• Support Opportunities: Scholarships in Brazil - Post-Doctoral