Crystal structure of saposin B reveals a dimeric shell for lipid binding.
Saposin B is a small, nonenzymatic glycosphingolipid activator protein required for the breakdown of cerebroside sulfates (sulfatides) within the lysosome. The protein can extract target lipids from membranes, forming soluble protein-lipid complexes that are recognized by arylsulfatase A. The crystal structure of human saposin B reveals an unusual shell-like dimer consisting of a monolayer of alpha-helices enclosing a large hydrophobic cavity. Although the secondary structure of saposin B is similar to that of the known monomeric members of the saposin-like superfamily, the helices are repacked into a different tertiary arrangement to form the homodimer. A comparison of the two forms of the saposin B dimer suggests that extraction of target lipids from membranes involves a conformational change that facilitates access to the inner cavity.
Ahn
Victoria E
VE
Department of Medical Biophysics, University of Toronto, ON, Canada M5G 2M9.
Faull
Kym F
KF
Whitelegge
Julian P
JP
Fluharty
Arvan L
AL
Privé
Gilbert G
GG
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D049231:Saposins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D049128:Sphingolipid Activator Proteins
D006023:Glycoproteins; C483345:PSAP protein, human; D049231:Saposins; D049128:Sphingolipid Activator Proteins