title: Crystal structures of human saposins C andD: implications for lipid recognition and membrane interactions.
abstract: Human saposins are essential proteins required for degradation of sphingolipids and lipid antigen presentation. Despite the conserved structural organization of saposins, their distinct modes of interaction with biological membranes are not fully understood. We describe two crystal structures of human saposin C in an "open" configuration with unusual domain swapped homodimers. This form of SapC dimer supports the "clip-on" model for SapC-induced vesicle fusion. In addition, we present the crystal structure of SapD in two crystal forms. They reveal the monomer-monomer interface for the SapD dimer, which was confirmed in solution by analytical ultracentrifugation. The crystal structure of SapD suggests that side chains of Lys10 and Arg17 are involved in initial association with the preferred anionic biological membranes by forming salt bridges with sulfate or phosphate lipid headgroups.
authors.affiliation: Institut für Chemie und Biochemie, Kristallographie, Freie Universität Berlin, Takustr. 6, 14195 Berlin, Germany.
authors.forename: Maxim
authors.initials: M
authors.lastname: Rossmann
authors.forename: Robert
authors.initials: R
authors.lastname: Schultz-Heienbrok
authors.forename: Joachim
authors.initials: J
authors.lastname: Behlke
authors.forename: Natascha
authors.initials: N
authors.lastname: Remmel
authors.forename: Claudia
authors.initials: C
authors.lastname: Alings
authors.forename: Konrad
authors.initials: K
authors.lastname: Sandhoff
authors.forename: Wolfram
authors.initials: W
authors.lastname: Saenger
authors.forename: Timm
authors.initials: T
authors.lastname: Maier
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry; D019281:Dimerization; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D050356:Lipid Metabolism; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010843:Pichia / Q000235:genetics; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification; D049231:Saposins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D017386:Sequence Homology, Amino Acid
chemical_list: D011994:Recombinant Proteins; D049231:Saposins; D003545:Cysteine