Dynamics of lipid displacement inside the hydrophobic cavity of a nonspecific lipid transfer protein from Solanum melongena

Abstract

Nonspecific lipid transfer proteins are multifunctional and multispecific seed proteins with a characteristic hydrophobic cavity that runs form N-terminal to the C-terminal end. They are capable of binding and transferring different lipid molecules by means of their hydrophobic cavity. Apart from the cavity, lipid molecules bind and interact at key positions on the nsLTP surface as well. The plasticity of the hydrophobic cavity is an unusual property, considered as the primary lipid binding site. Here, we report a crystal structure of nsLTP from Solanum melongena with two lauric acid molecules bound inside the cavity. It has been observed that the extent of the N-terminal entry point and plasticity of the cavity can be extended, upon binding of one or two lipid molecules inside the cavity. The MD simulation further revealed that the lipid molecule shows high mobility inside the cavity and interestingly, was able to change its orientation. An alternate lipid entry site adjacent to the N-terminal end was uncovered during simulation and Arg-84 was implicated to be a potential regulatory residue aside from Tyr-59. Collectively, this study helps to understand that changes in orientation of the lipid inside the cavity could occur intermittently besides entering the cavity via tail-in-mechanism.

Communicated by Ramaswamy H. Sarma

Keywords:

• Cavity plasticity
• lipid transfer protein
• lipid orientation
• relative binding affinities

Acknowledgements

We thank Mr Ravi Kant Pal for providing support with data collection at Rigaku R-Axis IV, National Institute of Immunology, New Delhi. We would like to acknowledge the Department of Biotechnology, Govt. of India for the generous funding.

Disclosure statement

No potential conflict of interest was reported by the authors.

Accession number

The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.wwpdb.org (PDB ID code: 7W9A).

Author’s contributions

Z.K.M and D.M.S conceived and designed the experiments, Z.K.M, U.K and D.J carried out extraction and purification, Z.K.M and A.K determined structure, Z.K.M performed the MD simulation, Z.K.M and A.K carried out molecular docking and binding energy estimation, U.K and D.J carried out TNS based assay, Z.K.M and D.M.S analyzed the data and wrote the manuscript.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.