Heckenberger et al. (2008) Pre-Columbian Uranism Anthropogenic Landscapes and the Future of the Ama

Heckenberger et al. (2008) Pre-Columbian Uranism Anthropogenic Landscapes and the Future of the Ama

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toward the extracellular side of the pore, further increasing the energetic cost for ions to traverse this region. The series of TM1-TM2 tilts and TM3 rotations leads to the formation of a large 10 to 12 Å × 20 Å conductive pathway lined by the TM3a and TM3b segments; preliminary MD simulations show conduction of both cations and anions through this pore (fig. S6). These per- meation pathway cross sections underlie the sim- ilarities between the open model and the MscS crystal structure ( 12 , 13 ). Except for the narrow- ing at the intracellular end of its pore (Fig. 4C, arrows), the crystal structure could, in principle, support ion conduction and thus might represent an inactivated/desensitized conformation after opening. The structural rearrangements described here demonstrate a gating mechanism that is dis- tinct from that of MscL ( 14 , 17 , 18 ) but confirms the critical role of helix tilting in transducing bilayer deformations to generate an aqueous pathway through the membrane. Note added in proof: A recent model of open MscS ( 42 ), based on computation and single- channel analyses, is in agreement with the present conformation of TM3 (Fig. 2). References and Notes 1. N. Levina et al ., EMBO J. 18 , 1730 (1999). 2. A. P. Christensen, D. P. Corey, Nat. Rev. Neurosci. 8 , 510 (2007). 3. B. Martinac, Cell. Physiol. Biochem. 11 , 61 (2001). 4. C. D. Pivetti et al ., Microbiol. Mol. Biol. Rev. 67 , 66 (2003). 5. K. Yoshimura, T. Nomura, M. Sokabe, Biophys. J. 86 , 2113 (2004). 6. T. Nomura, M. Sokabe, K. Yoshimura, Biophys. J. 91 , 2874 (2006). 7. F. Maingret, A. J. Patel, F. Lesage, M. Lazdunski, E. Honore, J. Biol. Chem. 275 , 10128 (2000). 8. K. Hayakawa, H. Tatsumi, M. Sokabe, J. Cell Sci. 121 , 496 (2008). 9. P. Gottlieb et al ., Pflugers Arch. 455 , 1097 (2008). 10. K. Y. Kwan et al ., Neuron 50 , 277 (2006). 11. G. Chang, R. H. Spencer, A. T. Lee, M. T. Barclay, D. C. Rees, Science 282 , 2220 (1998). 12. R. B. Bass, P. Strop, M. Barclay, D. C. Rees, Science 298 , 1582 (2002). 13. S. Steinbacher, R. Bass, P. Strop, D. C. Rees, Structures of the Prokaryotic Mechanosensitive Channels MscL and MscS (Current Topics in Membranes. Mechanosensitive Ion Channels, Part A, Elsevier, New York, 2007), pp. 1 24. 14. E. Perozo, D. M. Cortes, P. Sompornpisut, A. Kloda, B. Martinac, Nature 418 , 942 (2002). 15. E. Perozo, A. Kloda, D. M. Cortes, B. Martinac, Nat. Struct. Biol. 9 , 696 (2002). 16. S. Sukharev, M. Betanzos, C. S. Chiang, H. R. Guy, Nature 409 , 720 (2001). 17. J. Gullingsrud, K. Schulten, Biophys. J. 85 , 2087 (2003). 18. M. Betanzos, C. S. Chiang, H. R. Guy, S. Sukharev, Nat. Struct. Biol. 9 , 704 (2002). 19. E. Perozo, A. Kloda, D. M. Cortes, B. Martinac, J. Gen. Physiol.
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This note was uploaded on 10/22/2010 for the course ASB 326 taught by Professor Falconer during the Fall '08 term at ASU.

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Heckenberger et al. (2008) Pre-Columbian Uranism Anthropogenic Landscapes and the Future of the Ama

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