Solution structure of a mammalian pcb-binding protein in complex with a pcb

Nature

Solution structure of a mammalian pcb-binding protein in complex with a pcb"


Play all audios:

Loading...

ABSTRACT 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. Access


through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal


Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices


may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support


SIMILAR CONTENT BEING VIEWED BY OTHERS BIOCOORDINATION REACTIONS IN COPPER(II) IONS AND PHOSPHOCHOLINE SYSTEMS INCLUDING PYRIMIDINE NUCLEOSIDES AND NUCLEOTIDES Article Open access 04 July


2023 AN ELECTRON TRANSFER COMPETENT STRUCTURAL ENSEMBLE OF MEMBRANE-BOUND CYTOCHROME P450 1A1 AND CYTOCHROME P450 OXIDOREDUCTASE Article Open access 08 January 2021 XFEL CRYSTALLOGRAPHY


REVEALS CATALYTIC CYCLE DYNAMICS DURING NON-NATIVE SUBSTRATE OXIDATION BY CYTOCHROME P450BM3 Article Open access 12 March 2025 REFERENCES * Safe, S., Toxicology, structure-function


relationship, and human and environmental health impacts of polychlorinated biphenyls: progress and problems. _Envir. Hlth Perspect._ 100, 259–268 (1993). Article  CAS  Google Scholar  *


Brandt, I. _et al_. Target cells for the polychlorinated biphenyl metabolite 4,4′-bis(methylsulfonyl)-2,2′,5,5′-tetrachlorobiphenyl in lung and kidney. _Drug Metab. Disposit._ 13, 490–496


(1985). CAS  Google Scholar  * Lund, J. _et al_. Target cells for the polychlorinated biphenyl metabolite 4,4′-bis(methylsulfonyl)-2,2′,5,5′-tetrachlorobiphenyl.Characterization of high


affinity binding in rat and mouse lung cytosol. _Molec. Pharmacol._ 27, 314–323 (1985). CAS  Google Scholar  * Gillner, M. _et al_. The binding of methylsulfonyl-polychloro-biphenyls to


uteroglobin. _J. Steroid Biochem._ 31, 27–33 (1988). Article  CAS  Google Scholar  * Brandt, I. & Bergman, Å. Bronchial mucosal and kidney cortex affinity of 4- and 4,4′-substituted


sulphur-containing derivatives of 2,2′-5,5′-tetrachlorobiphenyl in mice. _Chem. Biol. Interact._ 34, 47–55 (1981). Article  CAS  Google Scholar  * Lund, J., Devereux, T., Glaumann, H. &


Gustafsson, J.-Å. Cellular and subcellular localization of a binding protein for polychlorinated biphenyls in rat lung. _Drug Metab. Disposit._ 16, 590–599 (1988). CAS  Google Scholar  *


Lund, J., Nordlund, L. & Gustafsson, J.-A. Partial purification of a binding protein for polychlorinated biphenyls from rat lung cytosol: physicochemical and immunochemical


characterization. _Biochemistry_ 27, 7895–7901 (1988). Article  CAS  Google Scholar  * Chaloupka, K., Krishnan, V. & Safe, S. Polynuclear aromatic hydrocarbon carcinogens as


antiestrogens in MCF-7 human breast cancer cells: role of the Ah receptor. _Carcinogenesis_ 13, 2233–2239 (1992). Article  CAS  Google Scholar  * Krishnan, V. & Safe, S. Polychlorinated


biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), and dibenzofurans (PCDFs) as antiestrogens in MCF-7 human breast cancer cells: quantitative structure-activity relationships. _Toxicology appl.


Pharmac._ 120, 55–61 (1993). Article  CAS  Google Scholar  * Safe, S. Male sexual development in “a sea of oestrogen”. _Lancet_ 342, 125 (1993). CAS  PubMed  Google Scholar  * Korach, K.S.,


Sarver, P., Chae, K., McLachlan, J.A. & McKinney, J.D. Estrogen receptor-binding activity of polychlorinated hydroxybiphenyls: conformationally restricted structural probes. _Molec.


Pharm._ 33, 120–126 (1988). CAS  PubMed  Google Scholar  * Shigematsu, N. _et al_. Respiratory involvement in polychorinated biphenyls poisoning. _Environ. Res._ 16, 92–100 (1978). Article 


CAS  Google Scholar  * Haraguchi, H., Kuroki, H., Masuda, Y. & Shigematsu, N. Determination of methylthio and methylsulphone polychlorinated biphenyls in tissues of patients with


‘yusho’. _Food Chem. Toxicol._ 22, 283–288 (1984). Article  CAS  Google Scholar  * Morize, I. _et al_. Refinement of the C 2 2 21 crystal form of oxidized uteroglobin at 1.34 Ångstroms


resolution. _J. molec. Biol._ 194, 725–739 (1987). Article  CAS  Google Scholar  * Bally, R. & Delettre, J. Structure and refinement of the oxidized P2 1 form of uteroglobin at 1.64


Ångströms resolution. _J. molec. Biol._ 206, 153–170 (1989). Article  CAS  Google Scholar  * Umland, T.C. _et al_. Refined structure of rat Clara cell 17 kDa protein at 3.0 Ångströms


resolution. _J. molec. Biol._ 224, 442–448 (1992). Article  Google Scholar  * Umland, T.C. _et al_. Structure of a human Clara cell phospholibid-binding protein-ligand complex at 1.9 Å


resolution. _Nature struct. Biol._ 1, 538–545 (1994). Article  CAS  Google Scholar  * Peter, W., Brüller, H.-J., Vriend, G., Beato, M. & Suske, G. Identification of residues essential


for progesterone binding to uteroglobin by site-directed mutagenesis. _J. Steroid Biochem._ 38, 27–33 (1991). Article  CAS  Google Scholar  * Dunkel, R., Vriend, G., Beato, M. & Suske,


G. Progesterone binding to uteroglobin: two alternative conformations of the ligand. _Prot. Engng._ 8, 71–79 (1995). Article  CAS  Google Scholar  * Peter, W. _et al_. Interchain cysteine


bridges control entry of progesterone to the central cavity of the uteroglobin dimer. _Prot Engng._ 5, 351–359 (1992). Article  CAS  Google Scholar  * Wüthrich, K. _NMR of proteins and


nucleic acids_. (Wiley, New York; 1986). Book  Google Scholar  * Roberts, G.C.K. (Ed.), _NMR of macromolecules_ (Oxford University Press; 1993). Google Scholar  * Brünger, A. _X-PLOR version


3.1. A system for X-ray crystallography and NMR_ (Yale Univeristy Press; 1992). Google Scholar  * Lee, B. & Richards, F.M. The interpretation of protein structures: estimation of static


accessibilities. _J. molec. Biol._ 55, 379–400 (1971). Article  CAS  Google Scholar  * Andersson, O., Nordlund-Möller, L., Barnes, H.J. & Lund, J. Heterologous expression of human


uteroglobin/polychlorinated biphenyl-binding protein. _J. biol. Chem._ 269, 19081–19087 (1994). CAS  PubMed  Google Scholar  * Nordlund-Möller, L. _et al_. Cloning, structure and expression


of a rat binding protein for polychlorinated biphenyls. _J. biol. Chem._ 265, 12690–12693 (1990). PubMed  Google Scholar  * Klasson Wehler, E., Bergman, Å. & Wachtmeister, C.A. Synthesis


of 4,4′-bis([3H]methylsulphonyl)-2,2′ 5,5′-tetrachlorobiphenyl. _J. labeled Compd. Radiopharm._ 20, 1407–1412 (1983). Article  CAS  Google Scholar  * Bergman, Å. & Wachtmeister, C.A.


Synthesis of methylthio- and methylsulphonylpolychlorobiphenyls via nucleophilic aromatic substitution of certain types of polychlorobiphenyls. _Chemosphere_ 7, 949–956 (1978). Article  CAS


  Google Scholar  * Rance, M. _et al_. Improved spectral resolution in COSY 1H spectra of proteins via double quantum filtering. _Biochem. biophys. Res. Comm._ 117, 479–485 (1983). Article 


CAS  Google Scholar  * Griesinger, C., Otting, G., Wüthrich, K. & Ernst, R.R. Clean TOCSY for 1H spin system identification in proteins. _J. Am. chem. Soc._ 110, 7870–7872 (1988).


Article  CAS  Google Scholar  * Macura, A. & Ernst, R.R. Elucidation of crossrelaxation in liquids by 2D NMR spectroscopy. _Molec. Phys._ 41, 95–117 (1980). Article  CAS  Google Scholar


  * Davis, A.L., Keeler, J., Laue, R.D. & Moskau, D. Experiments for recording pure-absorption heteronuclear correlation spectra using pulsed field gradients. _J. magn. Reson._ 98,


207–216 (1992). CAS  Google Scholar  * Gronenborn, A.M., Bax, A., Wingfield, P.T. & Clore, G.M. A powerful method of sequential proton resonance assignment in proteins using relayed


15N-1H multiple quantum coherence spectroscopy. _FEBS Lett._ 243, 93–98 (1989). Article  CAS  Google Scholar  * Bax, A., Clore, G.M. & Gronenborn, A.M. 1H-1H Correlation via isotropic


mixing of 13C magentization, a new three-dimensional approach for assigning 1H and 13C spectra of 13C-enriched proteins. _J. magn. Reson._ 88, 425–431 (1990). CAS  Google Scholar  * Kay,


L.E., Xu, G.-Y., Singer, A.U., Muhandiram, D.R. & Forman-Kay, J.D. A gradient-enhanced HCCH-TOCSY experiment for recording side-chain 1H and 13C correlation in H2O samples of proteins.


_J. magn. Reson._ B 101, 333–337 (1993). Article  Google Scholar  * Bax, A. _et al_. Practical aspects of proton-carbon-carbon-proton three-dimesnional spectroscopy of 13C-labeled proteins.


_J. magn. Reson._ 87, 620–627 (1990). CAS  Google Scholar  * Wider, G. & Wüthrich, K. A simple experimental scheme using pulsed field gradients for coherence-pathway rejection and


solvent suppression in phase-sensitive heteronuclear correlation spectra. _J. magn. Reson._ B 102, 239–241 (1993). Article  Google Scholar  * Kuboniwa, H., Grzesiek, S., Delaglio, F. &


Bax, A. Measurement of HN-Hα J couplings in calcium-free calmodulin using new 2D and 3D water-flip-back methods. _J. biol. NMR_ 4, 871–878 (1994). Article  CAS  Google Scholar  * Archer,


S.J., Ikura, M., Torchia, D.A. & Bax, A. An alternative 3D NMR technique for correlating backbone 15N with side chain Hβ resonances in larger proteins. _J. magn. Reson._ 95, 636–641


(1991). CAS  Google Scholar  * Vuister, G.W. & Bax, A. Measurement of two- and three-bond proton to methyl-carbon J couplings in proteins uniformly enriched with 13C. _J. magn. Reson._ B


102, 228–231 (1993). Article  Google Scholar  * Brown, S.C., Weber, P.L. & Mueller, L. Toward complete 1H NMR spectra in proteins. _J. magn. Reson._ 77, 166–169 (1988). CAS  Google


Scholar  * Nilges, M. A calculation strategy for the structure determination of symmetric dimers by 1H NMR. _Proteins_ 17, 297–309 (1993). Article  CAS  Google Scholar  * Koning, T.M.G.,


Boelens, R. & Kaptein, R. Calculation of the nuclear Overhauser effect and the determination of proton-proton distances in the presence of internal motions. _J. magn. Reson._ 90, 111–123


(1990). CAS  Google Scholar  * Wagner, G., Hyberts, S.G. & Havel, T.F. NMR structure determination in solution: a critique and comparison with X-ray crystallography. _A. Rev. Biophys.


biomol. Struct._ 21, 167–198 (1992). Article  CAS  Google Scholar  * Clore, G.M., Bax, A. & Gronenborn, A.M. Stereospecific assignment of β-methylene protons in larger proteins using 3D


15N-separated Hartmann-Hahn and 13C-separated rotating frame Overhauser spectroscopy. _J. biomol. NMR_ 1, 13–22 (1991). Article  CAS  Google Scholar  * Vuister, G.W. & Bax, A.


Quantitative J correlation: a new approach for measuring homonuclear three-bond J(HNHα) coupling constants in 15N-enriched proteins. _J. Am. chem. Soc._ 115, 7772–7777 (1993). Article  CAS 


Google Scholar  * Ludvigsen, S. & Poulsen, F.M. Positive φ-angles in proteins by nuclear magnetic resonance spectroscopy. _J. biol. NMR_ 2, 227–233 (1991). Article  Google Scholar  *


Vuister, G.W., Yamazaki, T., Torchia, D.A. & Bax, A. Measurement of two- and three-bond 13C-1H J couplings to the Cδ carbons of leucine residues in staphylococcal nuclease. _J. biol.


NMR_ 3, 297–306 (1993). Article  CAS  Google Scholar  * Zuiderweg, E.R.P., Boelens, R. & Kaptein, R. Stereospecific assignments of 1H-NMR methyl lines and conformation of valyl side


chains in the lac repressor head piece. _Biopolymers_ 24, 601–611 (1985). Article  CAS  Google Scholar  * Hargittai, I. in _The chemistry of sulphones and sulphoxides_ (eds Patai, S.,


Rappoport, Z. & Stirling, C. J. M.) 33 (John Wiley & Sons; 1988). Google Scholar  * Kraulis, P.J. MOLSCRIPT: a program to produce both detailed and schematic plots of protein


structures. _J. appl. Crystallogr._ 24, 946–950 (1991). Article  Google Scholar  * Bacon, D.J. & Anderson, W.F. A fast algorithm for rendering spacefilling molecule pictures. _Molec.


Graphics_ 6, 219–220 (1988). Article  Google Scholar  Download references AUTHOR INFORMATION Author notes * Henry J. Barnes Present address: Immune Complex Corporation, 11099 N.Torrey Pines


Road Suite 240, La Jolla, California, 92037, USA AUTHORS AND AFFILIATIONS * Center for Structural Biochemistry, Karolinska Institutet NOVUM, S-14157, Huddinge, Sweden Torleif Härd *


Department of Medical Nutrition, Karolinska Institutet NOVUM, S-14157, Huddinge, Sweden Henry J. Barnes, Jan-Åke Gustafsson & Johan Lund * Department of Environmental Chemistry,


Wallenberg Laboratory, Stockholm University, S-106 91, Stockholm, Sweden Christina Larsson Authors * Torleif Härd View author publications You can also search for this author inPubMed Google


Scholar * Henry J. Barnes View author publications You can also search for this author inPubMed Google Scholar * Christina Larsson View author publications You can also search for this


author inPubMed Google Scholar * Jan-Åke Gustafsson View author publications You can also search for this author inPubMed Google Scholar * Johan Lund View author publications You can also


search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Härd, T., Barnes, H., Larsson, C. _et al._ Solution


structure of a mammalian PCB-binding protein in complex with a PCB. _Nat Struct Mol Biol_ 2, 983–989 (1995). https://doi.org/10.1038/nsb1195-983 Download citation * Received: 11 August 1995


* Accepted: 20 September 1995 * Issue Date: 01 November 1995 * DOI: https://doi.org/10.1038/nsb1195-983 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this


content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative


Trending News

Next £49 sandals in four 'elegant' colours 'go with any outfit'

THE TAN BROWN STANDARD/WIDE FIT FOREVER COMFORT LEATHER ROUND TOE CROSS-OVER SLINGBACK PLATFORM WEDGES HAVE A LARGE HEEL...

Film blog | film | the guardian

This year's festival opened with a film which would have looked more at home in the marche - that great sanctuary o...

Future large hydropower dams impact global freshwater megafauna

ABSTRACT Dam construction comes with severe social, economic and ecological impacts. From an ecological point of view, h...

Cfpb director: beware of counterfeit stimulus checks

Fraudsters across the U.S. are sending counterfeit stimulus checks to people in an attempt to con them into paying an ad...

Former rep. Robert l. F. Sikes, 88; florida political boss for 38 years

CRESTVIEW, Fla. — Former Rep. Robert L.F. Sikes, a 38-year member of Congress who dominated Florida Panhandle politics f...

Latests News

Solution structure of a mammalian pcb-binding protein in complex with a pcb

ABSTRACT Metabolites of polychlorinated biphenyls (PCBs) bind with high affinity to uteroglobin, a small homodimeric pro...

Vikings season 5: will alfred kill ivar? Why is alfred important?

WILL ALFRED KILL IVAR IN VIKINGS SEASON 5? It seems very unlikely that Alfred (played by Ferdia Walsh-Peelo) will kill I...

Students' science savvy brings rewards | science news

Science News was founded in 1921 as an independent, nonprofit source of accurate information on the latest news of scien...

Bar owner speaks out after clips emerge of drivers fighting in traffic mayhem

THE LATEST MOVE ON DEANSGATE WAS BRANDED AN 'ABSOLUTE JOKE' 06:28, 18 Dec 2024Updated 10:07, 19 Dec 2024 The o...

Tip of the week: make vacation memories last

TALK ABOUT YOUR TRIP. Though you might think creating a slide show or video is “cheesy,” showing images of or simply tel...

Top