Specificity of Lipoprotein Chaperones for the Characteristic Lipidated Structural Motifs of their Cognate Lipoproteins.
Lipoprotein-binding chaperones mediate intracellular transport of lipidated proteins and determine their proper localisation and functioning. Understanding of the exact structural parameters that determine recognition and transport by different chaperones is of major interest. We have synthesised several lipid-modified peptides, representative of different lipoprotein classes, and have investigated their binding to the relevant chaperones PDEδ, UNC119a, UNC119b, and galectins-1 and -3. Our results demonstrate that PDEδ recognises S-isoprenylated C-terminal peptidic structures but not N-myristoylated peptides. In contrast, UNC119 proteins bind only mono-N-myristoylated, but do not recognise doubly lipidated and S-isoprenylated peptides at the C terminus. For galectins-1 and -3, neither binding to N-acylated, nor to C-terminally prenylated peptides could be determined. These results shed light on the specificity of the chaperone-mediated cellular lipoprotein transport systems.
Department of Chemical Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227, Dortmund, Germany.
Tom
T
Mejuch
Department of Chemical Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227, Dortmund, Germany.
Hilde
H
van Hattum
Department of Chemical Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227, Dortmund, Germany.
Gemma
G
Triola
Department of Structural Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227, Dortmund, Germany.
Mamta
M
Jaiswal
Department of Chemical Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227, Dortmund, Germany. herbert.waldmann@mpi-dortmund.mpg.de.|Department of Chemistry and Chemical Biology, Technical University of Dortmund, Otto-Hahn-Strasse 6, 44227, Dortmund, Germany. herbert.waldmann@mpi-dortmund.mpg.de.
Herbert
H
Waldmann
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000737:chemistry / Q000378:metabolism; D037483:Galectin 1 / Q000737:chemistry / Q000378:metabolism; D037502:Galectin 3 / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008074:Lipoproteins / Q000737:chemistry* / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding
D048868:Adaptor Proteins, Signal Transducing; D037483:Galectin 1; D037502:Galectin 3; D008074:Lipoproteins; D018832:Molecular Chaperones; D010455:Peptides; C098032:UNC119 protein, human; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6
fluorescent probes; peptides; protein modifications; protein-protein interactions