How arginine crosses across the prokaryotic and eukaryotic membranes: a mechanistic study by umbrella sampling approach

Arginine, as a semiessential amino acid, plays a crucial role in various cellular functions. Both normal and cancerous cells are required arginine for their cellular physiology. A great deal of the arginine is transported via a type of membrane transporter called cationic amino acid transporter (CAT) from the extracellular to cytoplasmic side of the cells. This study is purposed at investigating the key amino acids during arginine transportation through prokaryotic and eukaryotic CAT proteins.The structure coordinates of p-CAT is obtained from RCSB (PDB Id 6F34). The e-CAT structure was modeled using MODELLER software based on p-CAT as template. Since the CATs are membrane proteins, appropriate lipid bilayers were built around the target proteins by using CHARMM-GUI web server. Thereafter, MD simulations were carried out for prokaryotic and eukaryotic CAT for 600 and 1000 ns, respectively. The umbrella sampling approach was utilized for calculation of free energy differences of arginine transport through each CAT.Based on the potential of mean force (PMF) analyses, arginine binds to the prokaryotic CAT more tightly than the eukaryotic one. Hence, it seems that arginine passes across the e-CAT more comfortable than the p-CAT. In addition, H-bond analysis showed that the residues Asp237, Glu115, Ser321, Glu245, Lys19 in p-CAT and the residues Asp270, Glu185, Ser22, Asp20, Arg27 in e-CAT are the main contributors in interaction with arginine. The findings obtained here at molecular level, might shed light on better understanding of the actual mechanism(s) by which arginine permeate through the membranes of the prokaryotic and eukaryotic cells.

کلیدواژه ها:

Cationic amino acid transporter ، Molecular dynamics simulation ، Umbrella sampling