title: The closed conformation of the LDL receptor is destabilized by the low Ca(++) concentration but favored by the high Mg(++) concentration in the endosome.
abstract: The LDL receptor (LDLR) internalizes LDL and VLDL particles. In the endosomes, it adopts a closed conformation important for recycling, by interaction of two modules of the ligand binding domain (LR4-5) and a β-propeller motif. Here, we investigate by SPR the interactions between those two modules and the β-propeller. Our results indicate that the two modules cooperate to bind the β-propeller. The binding is favored by low pH and by high [Ca(++)]. Our data show that Mg(++), at high concentration in the endosome, favors the formation of the closed conformation by replacing the structuring effect of Ca(++) in LR5. We propose a sequential model of LDL release where formation of the close conformation follows LDL release.
authors.affiliation: Biocomputation and Complex Systems Physics Institute (BIFI)-Joint Unit BIFI-IQFR (CSIC), Universidad de Zaragoza, Zaragoza, Spain; Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain; Aragon Health Research Institute (IIS Aragón), Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Martínez-Oliván
authors.affiliation: Biocomputation and Complex Systems Physics Institute (BIFI)-Joint Unit BIFI-IQFR (CSIC), Universidad de Zaragoza, Zaragoza, Spain; Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Xabier
authors.initials: X
authors.lastname: Arias-Moreno
authors.affiliation: Biocomputation and Complex Systems Physics Institute (BIFI)-Joint Unit BIFI-IQFR (CSIC), Universidad de Zaragoza, Zaragoza, Spain; Aragon Health Research Institute (IIS Aragón), Universidad de Zaragoza, Zaragoza, Spain; Fundación ARAID, Diputación General de Aragón, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Hurtado-Guerrero
authors.affiliation: Biocomputation and Complex Systems Physics Institute (BIFI)-Joint Unit BIFI-IQFR (CSIC), Universidad de Zaragoza, Zaragoza, Spain; Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain; Aragon Health Research Institute (IIS Aragón), Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: José Alberto
authors.initials: JA
authors.lastname: Carrodeguas
authors.affiliation: Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (IBV-CSIC), Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Miguel-Romero
authors.affiliation: Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (IBV-CSIC), Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Marina
authors.affiliation: Biocomputation and Complex Systems Physics Institute (BIFI)-Joint Unit BIFI-IQFR (CSIC), Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Bruscolini
authors.affiliation: Biocomputation and Complex Systems Physics Institute (BIFI)-Joint Unit BIFI-IQFR (CSIC), Universidad de Zaragoza, Zaragoza, Spain; Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain; Aragon Health Research Institute (IIS Aragón), Universidad de Zaragoza, Zaragoza, Spain. Electronic address: jsancho@unizar.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Sancho
mesh_terms: D020816:Amino Acid Motifs / Q000187:drug effects; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D011992:Endosomes / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008074:Lipoproteins / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism* / Q000494:pharmacology; D008958:Models, Molecular; D055550:Protein Stability / Q000187:drug effects; D017434:Protein Structure, Tertiary / Q000187:drug effects; D011973:Receptors, LDL / Q000737:chemistry* / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D008074:Lipoproteins; D011973:Receptors, LDL; D004815:Epidermal Growth Factor; D008274:Magnesium; D002118:Calcium
keywords: Binding; Endosome; Low density lipoprotein receptor; Surface plasmon resonance