Crystal structures of human saposins C andD: implications for lipid recognition and membrane interactions.
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.
Rossmann
Maxim
M
Institut für Chemie und Biochemie, Kristallographie, Freie Universität Berlin, Takustr. 6, 14195 Berlin, Germany.
Schultz-Heienbrok
Robert
R
Behlke
Joachim
J
Remmel
Natascha
N
Alings
Claudia
C
Sandhoff
Konrad
K
Saenger
Wolfram
W
Maier
Timm
T
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
D011994:Recombinant Proteins; D049231:Saposins; D003545:Cysteine