Solution structure of a mammalian PCB-binding protein in complex with a PCB.
Metabolites of polychlorinated biphenyls (PCBs) bind with high affinity to uteroglobin, a small homodimeric protein that also binds progesterone. We present the solution structure of the reduced form of rat uteroglobin in complex with a PCB methylsulphone, (MeSO2)2-TCB. The structure reveals the molecular basis for the accumulation of (MeSO2)2-TCB by uteroglobin. The structure also shows how ligand binding and release might be controlled by reduction/oxidation of two intermolecular disulphide bonds. Breakage of these bonds induces a local unfolding of the N- and C-termini and a separation of helices creating a channel into the binding site. These effects make the ligand binding cavity readily accessible to entry of the ligand.
Härd
T
T
Center for Structural Biochemistry, Karolinska Institutet, NOVUM, Huddinge, Sweden.
Barnes
H J
HJ
Larsson
C
C
Gustafsson
J A
JA
Lund
J
J
D000595:Amino Acid Sequence; D000818:Animals; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011078:Polychlorinated Biphenyls / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014598:Uteroglobin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D008024:Ligands; D011994:Recombinant Proteins; C044524:4,4'-bis(methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl; D014598:Uteroglobin; D011078:Polychlorinated Biphenyls