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Solution structure of a mammalian PCB-binding protein in complex with a PCB
T Härd1, H J Barnes, C Larsson
1Center for Structural Biochemistry, Karolinska Institutet, NOVUM, Huddinge, Sweden.
Nature Structural Biology
|November 1, 1995
Summary
Polychlorinated biphenyl (PCB) metabolites bind strongly to uteroglobin. Structural analysis reveals how disulfide bond reduction opens the protein, facilitating PCB metabolite entry and release.
Area of Science:
- Biochemistry
- Structural Biology
- Toxicology
Background:
- Uteroglobin is a small homodimeric protein known to bind progesterone.
- Metabolites of polychlorinated biphenyls (PCBs) exhibit high affinity binding to uteroglobin.
Purpose of the Study:
- To elucidate the molecular mechanism of PCB metabolite accumulation by uteroglobin.
- To determine the solution structure of reduced rat uteroglobin in complex with a PCB methylsulphone, (MeSO2)2-TCB.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy for solution structure determination.
- X-ray crystallography (implied by structure determination).
Main Results:
- The study presents the solution structure of reduced rat uteroglobin complexed with (MeSO2)2-TCB.
- The structure reveals the molecular basis for (MeSO2)2-TCB accumulation within uteroglobin.
- Reduction/oxidation of disulfide bonds controls ligand binding and release by altering protein conformation.
Conclusions:
- Ligand binding and release are regulated by the redox state of intermolecular disulfide bonds.
- Disulfide bond breakage leads to local unfolding and helix separation, creating an accessible channel to the binding site.
- This conformational change facilitates the entry and release of PCB metabolites from the uteroglobin binding cavity.