Abstract
The fatty acid-binding proteins L-BABP and Rep1-NCXSQ bind to anionic lipid membranes by electrostatic interactions. According to Molecular Dynamics (MD) simulations, the interaction of the protein macrodipole with the membrane electric field is a driving force for protein binding and orientation in the interface. To further explore this hypothesis, we studied the interactions of these proteins with cationic lipid membranes. As in the case of anionic lipid membranes, we found that both proteins, carrying a negative as well as a positive net charge, were bound to the positively charged membrane. Their major axis, those connecting the bottom of the β-barrel with the α-helix portal domain, were rotated about 180 degrees as compared with their orientations in the anionic lipid membranes. Fourier transform infrared (FTIR) spectroscopy of the proteins showed that the positively charged membranes were also able to induce conformational changes with a reduction of the β-strand proportion and an increase in α-helix secondary structure. Fatty acid-binding proteins (FABPs) are involved in several cell processes, such as maintaining lipid homeostasis in cells. They transport hydrophobic molecules in aqueous medium and deliver them into lipid membranes. Therefore, the interfacial orientation and conformation, both shown herein to be electrostatically determined, have a strong correlation with the specific mechanism by which each particular FABP exerts its biological function.
Highlights
Electrostatic interactions are recognized as major contributing forces for membrane binding of peripheral membrane proteins [1,2,3,4,5]
The functionality, or biological activity of these proteins is strongly defined by the orientation within the membrane anisotropic environment and this orientation is -to a large extent- defined by electrostatic interactions
We have previously studied the binding to lipid membranes of the chicken liver bile acid-binding protein [6], (L-BABP, PDB ID 1TVQ [7]) and the regulatory protein of the squid nerve sodium calcium exchanger [8], (ReP1-NCXSQ, PDB 3PPT [9])
Summary
Electrostatic interactions are recognized as major contributing forces for membrane binding of peripheral membrane proteins [1,2,3,4,5]. Using Poisson Boltzman mean field theory in a rigid protein representation and a continuum model for the membrane, Zamarreño et al [14] have shown the influence of dipole-field interactions on the orientation of the protein and on the strength of binding Those works strongly suggest that the interaction between the macrodipole of the proteins and the membrane electric field contributes to orientation and to the binding to the interface. Mulgrew-Nesbitt et al [5] have reviewed the relevance of the charge distribution rather than the net charge We put this hypothesis under a severe test: if the electrostatic binding and orientation of FABPs to lipid membranes is influenced by the dipole-field interaction, it should work for cationic lipid membranes. As a result of these studies, new knowledgement was acquired about the organization, phase behaviour, segregation of lipid components and properties of the electric double layer in cationic interfaces [20,21,22,23,24]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
