A Comparative Study of Human Saposins
AbstractSaposins are small proteins implicated in trafficking and loading of lipids onto Cluster of Differentiation 1 (CD1) receptor proteins that in turn present lipid antigens to T cells and a variety of T-cell receptors, thus playing a crucial role in innate and adaptive immune responses in humans. Despite their low sequence identity, the four types of human saposins share a similar folding pattern consisting of four helices linked by three conserved disulfide bridges. However, their lipid-binding abilities as well as their activities in extracting, transporting and loading onto CD1 molecules a variety of sphingo- and phospholipids in biological membranes display two striking characteristics: a strong pH-dependence and a structural change between a compact, closed conformation and an open conformation. In this work, we present a comparative computational study of structural, electrostatic, and dynamic features of human saposins based upon their available experimental structures. By means of structural alignments, surface analyses, calculation of pH-dependent protonation states, Poisson-Boltzmann electrostatic potentials, and molecular dynamics simulations at three pH values representative of biological media where saposins fulfill their function, our results shed light into their intrinsic features. The similarities and differences in this class of proteins depend on tiny variations of local structural details that allow saposins to be key players in triggering responses in the human immune system. View Full-Text
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Garrido-Arandia, M.; Cuevas-Zuviría, B.; Díaz-Perales, A.; Pacios, L.F. A Comparative Study of Human Saposins. Molecules 2018, 23, 422.
Garrido-Arandia M, Cuevas-Zuviría B, Díaz-Perales A, Pacios LF. A Comparative Study of Human Saposins. Molecules. 2018; 23(2):422.Chicago/Turabian Style
Garrido-Arandia, María; Cuevas-Zuviría, Bruno; Díaz-Perales, Araceli; Pacios, Luis F. 2018. "A Comparative Study of Human Saposins." Molecules 23, no. 2: 422.
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