Abstract
An extensive polymorphism analysis of pollen profilin, a fundamental regulator of the actin cytoskeleton dynamics, has been performed with a major focus in 3D-folding maintenance, changes in the 2-D structural elements, surface residues involved in ligands-profilin interactions and functionality, and the generation of conformational and lineal B- and T-cell epitopes variability.Our results revealed that while the general fold is conserved among profilins, substantial structural differences were found, particularly affecting the special distribution and length of different 2-D structural elements (i.e. cysteine residues), characteristic loops and coils, and numerous micro-heterogeneities present in fundamental residues directly involved in the interacting motifs, and to some extension these residues nearby to the ligand-interacting areas. Differential changes as result of polymorphism might contribute to generate functional variability among the plethora of profilin isoforms present in the olive pollen from different genetic background (olive cultivars), and between plant species, since biochemical interacting properties and binding affinities to natural ligands may be affected, particularly the interactions with different actin isoforms and phosphoinositides lipids species.Furthermore, conspicuous variability in lineal and conformational epitopes was found between profilins belonging to the same olive cultivar, and among different cultivars as direct implication of sequences polymorphism. The variability of the residues taking part of IgE-binding epitopes might be the final responsible of the differences in cross-reactivity among olive pollen cultivars, among pollen and plant-derived food allergens, as well as between distantly related pollen species, leading to a variable range of allergy reactions among atopic patients. Identification and analysis of commonly shared and specific epitopes in profilin isoforms is essential to gain knowledge about the interacting surface of these epitopes, and for a better understanding of immune responses, helping design and development of rational and effective immunotherapy strategies for the treatment of allergy diseases.
Highlights
Profilins are ubiquitous and abundant cytosolic proteins of 12– 15 kDa, found in all eukaryotic cells [1,2,3] and virus [4]
We used the Swiss-model server to identify the best possible template to build all profilin structures, finding high scores and very low E-values for the 1g5uA, 1cqa and 3nul templates retrieved from the Protein Data Bank (PDB) database and used for homology modeling (Table S1)
The identification of profilin sequences in databases has focused on data comparison searches for sequence homology within the open reading frames of profilin genes
Summary
Profilins are ubiquitous and abundant cytosolic proteins of 12– 15 kDa, found in all eukaryotic cells [1,2,3] and virus [4] They are key regulators of actin cytoskeleton dynamics through their interaction to monomeric actin (G actin), and to a plethora of actin-binding proteins, which involve poly-L-proline (PLP) stretches [5]. Profilins regulate the pools of G actin able to recharge newly depolymerized ADP-actin monomers with ATP and driving their assembly onto existing free barbed ends This function could be developed by several mechanisms, including simple monomer sequestration, catalytic enhancement of actin-bound adenine nucleotide exchange, and the coupling of monomer addition to the growing filament with ATP hydrolysis [6]. Profilin facilitates the activity of nucleators of actin polymerization [7]
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