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Science 1 November 1996:
Vol. 274. no. 5288, pp. 768 - 770
DOI: 10.1126/science.274.5288.768

Reports

Requirement of Rigid-Body Motion of Transmembrane Helices for Light Activation of Rhodopsin

David L. Farrens, * Christian Altenbach, Ke Yang, dagger Wayne L. Hubbell, ddagger H. Gobind Khorana ddagger

Conformational changes are thought to underlie the activation of heterotrimeric GTP-binding protein (G protein)-coupled receptors. Such changes in rhodopsin were explored by construction of double cysteine mutants, each containing one cysteine at the cytoplasmic end of helix C and one cysteine at various positions in the cytoplasmic end of helix F. Magnetic dipolar interactions between spin labels attached to these residues revealed their proximity, and changes in their interaction upon rhodopsin light activation suggested a rigid body movement of helices relative to one another. Disulfide cross-linking of the helices prevented activation of transducin, which suggests the importance of this movement for activation of rhodopsin.

D. L. Farrens, K. Yang, H. G. Khorana, Departments of Biology and Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
C. Altenbach and W. L. Hubbell, Jules Stein Eye Institute and Department of Chemistry, University of California, Los Angeles, CA 90095-7008, USA.
*   Present address: Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland, OR 97201, USA.

dagger    Present address: Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.

ddagger    To whom correspondence should be addressed.


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Conformational Changes in the Phosphorylated C-terminal Domain of Rhodopsin during Rhodopsin Arrestin Interactions.
O. G. Kisselev, M. A. Downs, J. H. McDowell, and P. A. Hargrave (2004)
J. Biol. Chem. 279, 51203-51207
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Analysis of the Third Transmembrane Domain of the Human Type 1 Angiotensin II Receptor by Cysteine Scanning Mutagenesis.
S. S. Martin, A. A. Boucard, M. Clement, E. Escher, R. Leduc, and G. Guillemette (2004)
J. Biol. Chem. 279, 51415-51423
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Structural Mimicry in Class A G Protein-coupled Receptor Rotamer Toggle Switches: THE IMPORTANCE OF THE F3.36(201)/W6.48(357) INTERACTION IN CANNABINOID CB1 RECEPTOR ACTIVATION.
S. D. McAllister, D. P. Hurst, J. Barnett-Norris, D. Lynch, P. H. Reggio, and M. E. Abood (2004)
J. Biol. Chem. 279, 48024-48037
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Optimal bundling of transmembrane helices using sparse distance constraints.
K. Sale, J.-L. Faulon, G. A. Gray, J. S. Schoeniger, and M. M. Young (2004)
Protein Sci. 13, 2613-2627
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The Hydrodynamic Properties of Dark- and Light-activated States of n-Dodecyl {beta}-D-Maltoside-solubilized Bovine Rhodopsin Support the Dimeric Structure of Both Conformations.
R. Medina, D. Perdomo, and J. Bubis (2004)
J. Biol. Chem. 279, 39565-39573
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"Induced-Fit" Mechanism for Catecholamine Binding to the {beta}2-Adrenergic Receptor.
R. Del Carmine, P. Molinari, M. Sbraccia, C. Ambrosio, and T. Costa (2004)
Mol. Pharmacol. 66, 356-363
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Modulation of Ligand Selectivity Associated with Activation of the Transmembrane Region of the Human Follitropin Receptor.
L. Montanelli, J. J. J. Van Durme, G. Smits, M. Bonomi, P. Rodien, E. J. Devor, K. Moffat-Wilson, L. Pardo, G. Vassart, and S. Costagliola (2004)
Mol. Endocrinol. 18, 2061-2073
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Preferential Formation of MT1/MT2 Melatonin Receptor Heterodimers with Distinct Ligand Interaction Properties Compared with MT2 Homodimers.
M. A. Ayoub, A. Levoye, P. Delagrange, and R. Jockers (2004)
Mol. Pharmacol. 66, 312-32