Article abstract
Nature Structural & Molecular Biology 16, 168 - 175 (2009)
Published online: 1 February 2009 | doi:10.1038/nsmb.1549
Helix movement is coupled to displacement of the second extracellular loop in rhodopsin activation
Shivani Ahuja1, Viktor Hornak2, Elsa C Y Yan3,6, Natalie Syrett4, Joseph A Goncalves2, Amiram Hirshfeld5, Martine Ziliox2, Thomas P Sakmar3, Mordechai Sheves5, Philip J Reeves4, Steven O Smith2 & Markus Eilers2
Abstract
The second extracellular loop (EL2) of rhodopsin forms a cap over the binding site of its photoreactive 11-cis retinylidene chromophore. A crucial question has been whether EL2 forms a reversible gate that opens upon activation or acts as a rigid barrier. Distance measurements using solid-state 13C NMR spectroscopy between the retinal chromophore and the 
4 strand of EL2 show that the loop is displaced from the retinal binding site upon activation, and there is a rearrangement in the hydrogen-bonding networks connecting EL2 with the extracellular ends of transmembrane helices H4, H5 and H6. NMR measurements further reveal that structural changes in EL2 are coupled to the motion of helix H5 and breaking of the ionic lock that regulates activation. These results provide a comprehensive view of how retinal isomerization triggers helix motion and activation in this prototypical G protein–coupled receptor.
- Departments of Physics and Astronomy, Stony Brook University, Stony Brook, New York 11794-5215, USA.
- Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York 11794-5215, USA.
- Laboratory of Molecular Biology and Biochemistry, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
- Department of Biological Sciences, University of Essex, Wivenhoe Park, Essex C04 3SQ, UK.
- Department of Organic Chemistry, The Weizmann Institute, Rehovot 76100, Israel.
- Present address: Department of Chemistry, Yale University, New Haven, Connecticut 06520, USA.
Correspondence to: Steven O Smith2 e-mail: steven.o.smith@sunysb.edu.
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