Computational study of ligand binding in lipid transfer proteins: Structures, interfaces, and free energies of protein‐lipid complexes

Abstract

Plant nonspecific lipid transfer proteins (nsLTPs) bind a wide variety of lipids, which allows them to perform disparate functions. Recent reports on their multifunctionality in plant growth processes have posed new questions on the versatile binding abilities of these proteins. The lack of binding specificity has been customarily explained in qualitative terms on the basis of a supposed structural flexibility and nonspecificity of hydrophobic protein-ligand interactions. We present here a computational study of protein-ligand complexes formed between five nsLTPs and seven lipids bound in two different ways in every receptor protein. After optimizing geometries in molecular dynamics calculations, we computed PoissonBoltzmann electrostatic potentials, solvation energies, properties of the protein-ligand interfaces, and estimates of binding free energies of the resulting complexes. Our results provide the first quantitative information on the ligand abilities of nsLTPs, shed new light into protein-lipid interactions, and reveal new features which supplement commonly held assumptions on their lack of binding specificity.

Identification of the ligand of Pru p 3, a peach LTP

“…Despite the considerable heterogeneity in their primary structure, all LTPs share a compact a-helical fold composed of four a-helices connected by short loops and a non-structured C-terminal tail. This fold is stabilized by eight conserved cysteine residues that form four disulfide bonds (Pacios et al 2012;Salcedo et al 2007;Salminen et al 2016). A characteristic tunnel-like cavity aligned with the long axis of the protein is formed by the space left within the helices.…”

Expression of LTP genes in response to saline stress in rice seedlings

“…Studies have examined the physiological role of LTP proteins (Carvalho and Gomes, 2007) to identify genetic isoforms through alignments in the data bank for phylogenetic analyses of different species (Boutrot et al, 2008;Wang et al, 2012) and to describe the structure of these proteins (Pacios et al, 2012). However, functional studies are also important for determining the differential expression of these genes using specific expression techniques such as real-time quantitative-polymerase chain reaction (RT-qPCR).…”

Estudio de la alergenicidad en Alt a 1, una proteína única de hongos

“…Der p 2 can bind LPS and substitute the homologous human MD-2 protein thereby promoting Th2 responses in mice via TLR4 signaling. LPS exposure seems to play a variable role in both promoting and inhibiting allergic sensitization (40). Der p 7 shows structural similarities to the LPS-binding protein and bind weakly the bacterial lipopeptide polymyxin B (41).…”

“…[18,40] The allergenic properties of Pru p 3 have been thoroughly studied [14][15][16][17] and its IgE epitopes have been characterized by using different techniques. [14] Figure 4 displays initial geometries of dimeric crystal structure of Pru p 3 [17] ("dimer1" in what follows) that has epitope residues at a location not suitable for IgE cross-linking (Figure 4 A), a dimer predicted by EPPIC [8] ("dimer2) with the proper orientation of epitope residues (Figure 4 C), the monomer (Figure 4 B), and the protein-palmitate complex (Figure 4 D).…”

“…The large hydrophobic cavity (tunnel) is one of the main features of nsLTPs. [18,40] This tunnel runs parallel to the larger a-helix and is flanked by the unstructured CÀterminal tail (Figure 4). In order to assess its flexibility, we computed along the MD simulation two distances between residues that are involved in the interaction with palmitate and have besides their side chains at opposite locations at both ends of the cavity (Figure 4 B and 4 D).…”