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A Comparative Study of Human Saposins.
Molecules 2018; 23(2)M

Abstract

Saposins 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.

Authors+Show Affiliations

Centro de Biotecnología y Genómica de Plantas (CBGP, UPM-INIA), Campus de Montegancedo-UPM, 28223 Madrid, Spain. maria.garrido@upm.es.Centro de Biotecnología y Genómica de Plantas (CBGP, UPM-INIA), Campus de Montegancedo-UPM, 28223 Madrid, Spain. bruno.czuviria@upm.es.Centro de Biotecnología y Genómica de Plantas (CBGP, UPM-INIA), Campus de Montegancedo-UPM, 28223 Madrid, Spain. araceli.diaz@upm.es. Departamento de Biotecnología-Biología Vegetal, ETSIAAB, Universidad Politécnica de Madrid (UPM), Ciudad Universitaria, 28040 Madrid, Spain. araceli.diaz@upm.es.Centro de Biotecnología y Genómica de Plantas (CBGP, UPM-INIA), Campus de Montegancedo-UPM, 28223 Madrid, Spain. luis.fpacios@upm.es. Departamento de Biotecnología-Biología Vegetal, ETSIAAB, Universidad Politécnica de Madrid (UPM), Ciudad Universitaria, 28040 Madrid, Spain. luis.fpacios@upm.es.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29443946

Citation

Garrido-Arandia, María, et al. "A Comparative Study of Human Saposins." Molecules (Basel, Switzerland), vol. 23, no. 2, 2018.
Garrido-Arandia M, Cuevas-Zuviría B, Díaz-Perales A, et al. A Comparative Study of Human Saposins. Molecules. 2018;23(2).
Garrido-Arandia, M., Cuevas-Zuviría, B., Díaz-Perales, A., & Pacios, L. F. (2018). A Comparative Study of Human Saposins. Molecules (Basel, Switzerland), 23(2), doi:10.3390/molecules23020422.
Garrido-Arandia M, et al. A Comparative Study of Human Saposins. Molecules. 2018 Feb 14;23(2) PubMed PMID: 29443946.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Comparative Study of Human Saposins. AU - Garrido-Arandia,María, AU - Cuevas-Zuviría,Bruno, AU - Díaz-Perales,Araceli, AU - Pacios,Luis F, Y1 - 2018/02/14/ PY - 2018/01/24/received PY - 2018/02/12/revised PY - 2018/02/13/accepted PY - 2018/2/15/entrez PY - 2018/2/15/pubmed PY - 2018/8/18/medline KW - electrostatic potentials KW - lipid-antigens KW - molecular dynamics KW - protein-ligand interactions KW - protein-membrane interactions KW - saposins JF - Molecules (Basel, Switzerland) JO - Molecules VL - 23 IS - 2 N2 - Saposins 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. SN - 1420-3049 UR - https://www.unboundmedicine.com/medline/citation/29443946/A_Comparative_Study_of_Human_Saposins L2 - http://www.mdpi.com/resolver?pii=molecules23020422 DB - PRIME DP - Unbound Medicine ER -