The computational analyses, molecular dynamics of fatty-acid transport mechanism to the CD36 receptor

Jihane Akachar,Rachid El Jaoudi,Catherine Etchebest,Azeddine Ibrahimi

doi:10.1038/s41598-021-01373-5

Jihane Akachar, Rachid El Jaoudi + Show 2 more

Open Access

https://doi.org/10.1038/s41598-021-01373-5

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Abstract

The transmembrane glycoprotein CD36, which is responsible of the metabolic disorders, and the elevated intake of fat induces lipid buildup, is a multifunctional scavenger receptor signaling those functions in high-affinity tissue uptake of long-chain fatty acids. In this study, we used series of molecular dynamics simulations of the wild type and mutants types K164A CD36 protein interacting with one palmitic acid (PLM) besides simulations of the wild type interacting with the three PLM to find out the mechanism of the functioning of the complex CD36/Fatty acids and the unraveling of the role of the mutation. Additionally we determined whether Lys164, mostly exposed to protein surface, played important roles in fatty acid uptake. These simulations revealed, the conformational changes induced by Lys164 residue and the altered interactions induced by the mutagenesis of surface lysine that was badly influencing the folding, utility, solubility, and stability form of the variant. Furthermore, Lys164 residue provided the structural basis of forming an opening at the region of principal portal for the dissociation of palmitic acid. The results of our simulations revealed hole two fatty acids found in CD36 cavity structure and it was the most preferred to CD36 structure stabilization.

Highlights

The transmembrane glycoprotein CD36, which is responsible of the metabolic disorders, and the elevated intake of fat induces lipid buildup, is a multifunctional scavenger receptor signaling those functions in high-affinity tissue uptake of long-chain fatty acids
The tridimensional structures of virtual mutant K164A ectodomain of CD36 predicted by using Swiss Model server to construct the homology model based on the crystal structure CD36-cysteine-rich interdomain region α (CIDRα) (PDB ID: 5LGD)
That the flexible motions of theses secondary structures in the distinct active states are quite dissimilar from CD36 wild type (WT) in absence of palmitic acid (PLM) and complexes CD36 WT-PLM and mutant type (MT)-PLM Fig. 3a–c

Summary

Introduction

The transmembrane glycoprotein CD36, which is responsible of the metabolic disorders, and the elevated intake of fat induces lipid buildup, is a multifunctional scavenger receptor signaling those functions in high-affinity tissue uptake of long-chain fatty acids. CD36 mediated FA uptake and signaling in CHO cells expressing mutant CD36 (K164), this can be related to that short-chainalkyl of FA mediated the FA in relative orientation and p osition[22,23] The second that it is in the surface of the pocket, the carboxyl group of the FA can compose electrostatic interactions with Lys-164, and this pathway followed by CD36 conformational deviation to activate FA uptake and/or signaling. We used a computational approach to construct a three-dimensional structural model we utilized molecular dynamic to identify fatty acid binding site, transport trajectory and rate Based on these computational studies, the structural analysis of Lys[164] mutagenesis with FA interaction in the binding protein pocket has been documented and exposed to influence FA transfer. This could be a target for discovering a new drug by finding new mechanisms of FA/CD36 regulation associated with obesity and/or type[2] diabetes

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