DOI: 10.1126/science.1089401 , 377 (2004); 303Science et al.W. Tecumseh Fitch,in a Nonhuman PrimateComputational Constraints on Syntactic Processing www.sciencemag.org (this information is current as of April 7, 2008 ):The following resources related to this article are available online at http://www.sciencemag.org/cgi/content/full/303/5656/377version of this article at: including high-resolution figures, can be found in the onlineUpdated information and services, http://www.sciencemag.org/cgi/content/full/303/5656/377/DC1 can be found at: Supporting Online Materialfound at: can berelated to this articleA list of selected additional articles on the Science Web sites http://www.sciencemag.org/cgi/content/full/303/5656/377#related-content http://www.sciencemag.org/cgi/content/full/303/5656/377#otherarticles, 5 of which can be accessed for free: cites 19 articlesThis article 49 article(s) on the ISI Web of Science. cited byThis article has been http://www.sciencemag.org/cgi/content/full/303/5656/377#otherarticles 4 articles hosted by HighWire Press; see: cited byThis article has been http://www.sciencemag.org/cgi/collection/psychologyPsychology : subject collectionsThis article appears in the following http://www.sciencemag.org/about/permissions.dtl in whole or in part can be found at: this articlepermission to reproduce of this article or about obtaining reprintsInformation about obtaining registered trademark of AAAS. is aScience2004 by the American Association for the Advancement of Science; all rights reserved. The title CopyrightAmerican Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by theScience on April 7, 2008 www.sciencemag.orgDownloaded fromFinally, the observation that the SRPGTPases behave as reciprocal GTPase acti-vating proteins (5) can now be understood tobe a consequence of the formation of a sharedcatalytic chamber between them. Indeed, thereciprocal hydrogen bonding between thebound nucleotides may itself be catalyticallyimportant. However, the structure of the com-plex also demonstrates how the initial engage-ment of the two proteins can function as alatch, in that a number of structural elements,including the bound nucleotides, contribute toan intricate interface that is unlikely to disso-ciate until two subsequent steps, signal pep-tide transfer followed by nucleotide hydroly-sis, occur. This kind of mechanism for the SRPGTPases is consistent with a process requiringassembly of multiple components, and it can bedistinguished from one in which the GTPasesact along a signaling pathway. Extending themetaphor, the GTP molecules themselves canbe imagined as “explosive bolts” in that they areintegral to the interface that holds the proteinstogether, and so promote transfer of the translat-ing ribosomal cargo, but that they also provide,by their hydrolysis, the “explosion” that dis-engages the components of the targeting com-plex (fig. S6). This conception of the role ofGTP is somewhat distinct from the classicGTPase switch model and provides insight intothe logic of the SRP GTPases that may be rel-evant to understanding other GTPases that func-tion in the assembly of cellular components.Note added in proof: A structure of asimilar complex of the SRP GTPases in adifferent crystal form was independently de-termined and is reported by Egea et al.(36).References and Notes1. R. J. Keenan, D. M. Freymann, R. M. Stroud, P. Walter,Annu. Rev. Biochem. 70, 755 (2001).2. H. D. Bernstein et al., Nature 340, 482 (1989).3. K. Ro¨misch et al., Nature 340, 478 (1989).4. J. D. Miller, H. Wilhelm, L. Gierasch, R. Gilmore, P.Walter, Nature 366, 351 (1993).5. T. Powers, P. Walter, Science 269, 1422 (1995).6. Q. A. Valent et al., EMBO J. 17, 2504 (1998).7. C. Moser, O. Mol, R. S. Goody, I. Sinning, Proc. Natl.Acad. Sci. U.S.A. 94, 11339 (1997).8. P. Peluso, S. O. Shan, S. Nock, D. Herschlag, P. Walter,Biochemistry 40, 15224 (2001).9. Y. Lu et al., EMBO J. 20, 6724 (2001).10. S. Padmanabhan, D. M. Freymann, Structure 9, 859(2001).11. P. J. Rapiejko, R. Gilmore, Cell 89, 703 (1997).12. W. Song, D. Raden, E. C. Mandon, R. Gilmore, Cell100, 333 (2000).13. D. M. Freymann, R. J. Keenan, R. M. Stroud, P. Walter,Nature 385, 361 (1997).14. P. J. Focia, H. Alam, T. Lu, U. D. Ramirez, D. M.Freymann, Proteins 54, 222 (2004).15. G. Montoya, C. Svensson, J. Luirink, I. Sinning, Nature385, 365 (1997).16. G. Montoya, K. Kaat, R. Moll, G. Scha¨fer, I. Sinning,Structure 8, 515 (2000).17. I. R. Vetter, A. Wittinghofer, Science 294, 1299(2001).18. I. V. Shepotinovskaya, D. M. Freymann, Biochim. Bio-phys. Acta 1597, 107 (2002).19. I. V. Shepotinovskaya, P. J. Focia, D. M. Freymann,Acta Crystallogr. D59, 1834 (2003).20. Materials and methods are available as supportingmaterial on Science Online.21. A. Perrakis, T. K. Sixma, K. S. Wilson, V. S. Lamzin, ActaCrystallogr. D53, 448 (1997).22. Sequence motifs are defined for T. aquaticus Ffh andFtsY in table S1.23. J. A. Newitt, H. D. Bernstein, Eur. J. Biochem. 245, 720(1997).24. D. M. Freymann, R. J. Keenan, R. M. Stroud, P. Walter,Nat. Struct. Biol. 6, 793 (1999).25. U. D. Ramirez et al., J. Mol. Biol. 320, 783 (2002).26. K. Scheffzek et al., Science 277, 333 (1997).27. J. J. Tesmer, D. M. Berman, A. G. Gilman, S. R. Sprang,Cell 89, 251 (1997).28. P. J. Rapiejko, R. Gilmore, Mol. Biol. Cell 5, 887(1994).29. T. Connolly, P. J. Rapiejko, R. Gillmore, Science 252,1171 (1991).30. E. de Leeuw et al., EMBO J. 19, 531 (2000).31. J. S. Millman, H. Y. Qi, F. Vulcu, H. D. Bernstein, D. W.Andrews, J. Biol. Chem. 276, 25982 (2001).32. J. D. Miller, H. D. Bernstein, P. Walter, Nature 367,657 (1994).33. S. R. Sprang, Annu. Rev. Biochem. 66, 639 (1997).34. H. Lu¨tcke, S. High, K. Ro¨misch, A. J. Ashford, B.Dobberstein, EMBO J. 11, 1543 (1992).35. R. M. Cleverley, L. M. Gierasch, J. Biol. Chem. 277,46763 (2002).36. P. F. Egea et al., Nature 427, 215 (2004).37. We thank C. W. Carter, S. McGovern, U. D. Ramirez,and S. R. Sprang for critical reading of this manu-script, and Panchika Prangkio for her contribution.This work was supported by grant GM58500 from theNIH. Portions of this work were performed at theDuPont-Northwestern-Dow Collaborative AccessTeam (DND-CAT ) Synchrotron Research Center, Sec-tor 5, and BioCARS, Sector 14, of the AdvancedPhoton Source (APS) at Argonne National Laboratory.Use of the APS was