Compact packing of lipocalin-type prostaglandin D synthase induced by binding of lipophilic ligands.
Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is a multi-functioning protein belonging to the lipocalin family, acting as a PGD(2)-synthesizing enzyme and as an extracellular transporter for small lipophilic molecules. In the present study, to clarify the conformational changes of lipocalin proteins induced by binding of lipophilic ligands, such as all-trans-retinoic acid (RA), bilirubin (BR) and biliverdin (BV), we measured small-angle X-ray scattering (SAXS) of L-PGDS and that of two other lipocalins, beta-lactoglobulin (betaLG) and retinol-binding protein (RBP). L-PGDS bound all three ligands with high affinity, while betaLG and RBP could bind only RA. The radius of gyration was estimated to be 19.4 A for L-PGDS, and 18.8 A for L-PGDS/RA, 17.3 A for L-PGDS/BR and 17.8 A for L-PGDS/BV complexes, indicating that L-PGDS became compact after binding of these ligands. Alternatively, the radius of gyration of betaLG and RBP was 20.3 and 26.2 A, respectively, and was almost the same before and after RA binding. Based on the SAXS data, we found that the compact packing upon binding ligands is a special feature of L-PGDS and it may be ascribed to the conformational flexibility of L-PGDS molecule itself, which underlies the high-affinity for its ligands.
Inoue
Katsuaki
K
Research & Utilization Division, Japan Synchrotron Radiation Research Institute, 1-1-1 Koto, Sayo, Hyogo, Japan.
Yagi
Naoto
N
Urade
Yoshihiro
Y
Inui
Takashi
T
D000818:Animals; D001663:Bilirubin / Q000737:chemistry / Q000378:metabolism; D001664:Biliverdine / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D019746:Intramolecular Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D007782:Lactoglobulins / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D054834:Lipocalins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D011487:Protein Conformation; D012177:Retinol-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D014212:Tretinoin / Q000737:chemistry / Q000378:metabolism
D007782:Lactoglobulins; D008024:Ligands; D054834:Lipocalins; D012177:Retinol-Binding Proteins; D014212:Tretinoin; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D001664:Biliverdine; D001663:Bilirubin