Ras activation by SOS: Allosteric regulation by altered fluctuation dynamics

Lars Iversen; Hsiung-Lin Tu; Wan-Chen Lin; Sune M. Christensen; Steven M. Abel; Jeff Iwig; Hung-Jen Wu; Jodi Gureasko; Christopher Rhodes; Rebecca S. Petit; Scott D. Hansen; Peter Thill; Cheng-Han Yu; Dimitrios Stamou; Arup K. Chakraborty; John Kuriyan; Jay T. Groves

doi:10.1126/science.1250373

Research Article

Ras activation by SOS: Allosteric regulation by altered fluctuation dynamics

Lars Iversen¹,*,†,
Hsiung-Lin Tu¹,*,
Wan-Chen Lin¹,
Sune M. Christensen¹,†,
Steven M. Abel²,‡,
Jeff Iwig³,
Hung-Jen Wu¹,§,
Jodi Gureasko³,‖,
Christopher Rhodes⁴,
Rebecca S. Petit¹,
Scott D. Hansen¹,
Peter Thill⁵,
Cheng-Han Yu⁶,¶,
Dimitrios Stamou⁷,
Arup K. Chakraborty²,⁵,⁸,⁹,¹⁰,¹¹,
John Kuriyan¹,³,¹²,
Jay T. Groves¹,⁶,¹²,¹³,#

¹Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
²Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
³Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
⁴Department of Mechanical Engineering, University of California, Berkeley, Berkeley, CA 94720, USA.
⁵Department of Chemistry, MIT, Cambridge, MA 02139, USA.
⁶Mechanobiology Institute, National University of Singapore, Singapore.
⁷Department of Chemistry and Nano-Science Center, University of Copenhagen, Copenhagen, Denmark.
⁸Department of Biological Engineering, MIT, Cambridge, MA 02139, USA.
⁹Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Cambridge, MA 02139, USA.
¹⁰Department of Physics, MIT, Cambridge, MA 02139, USA.
¹¹Institute for Medical Engineering and Science, MIT, Cambridge, MA 02139, USA.
¹²Physical Biosciences and Materials Sciences Divisions, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
¹³Berkeley Education Alliance for Research in Singapore, 1 Create Way, CREATE tower level 11, University Town, Singapore 138602.

↵#Corresponding author. E-mail: jtgroves{at}lbl.gov

↵* These authors contributed equally to this work and are listed in alphabetical order.

↵† Present address: Department of Chemistry, University of Copenhagen, Copenhagen, Denmark.
↵‡ Present address: Department of Chemical and Biomolecular Engineering, University of Tennessee, Knoxville, TN 37996, USA.
↵§ Present address: Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, USA.
↵‖ Present address: Epizyme, 400 Technology Square, Cambridge, MA 02139, USA.
↵¶ Present address: Department of Anatomy, The University of Hong Kong, Hong Kong.

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Science 04 Jul 2014:
Vol. 345, Issue 6192, pp. 50-54
DOI: 10.1126/science.1250373

Lars Iversen

1Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.

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Hsiung-Lin Tu

1Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.

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Wan-Chen Lin

1Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.

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Sune M. Christensen

1Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.

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Steven M. Abel

2Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.

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Jeff Iwig

3Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

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Hung-Jen Wu

1Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.

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Jodi Gureasko

3Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

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Christopher Rhodes

4Department of Mechanical Engineering, University of California, Berkeley, Berkeley, CA 94720, USA.

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Rebecca S. Petit

1Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.

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Scott D. Hansen

1Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.

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Peter Thill

5Department of Chemistry, MIT, Cambridge, MA 02139, USA.

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Cheng-Han Yu

6Mechanobiology Institute, National University of Singapore, Singapore.

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Dimitrios Stamou

7Department of Chemistry and Nano-Science Center, University of Copenhagen, Copenhagen, Denmark.

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Arup K. Chakraborty

2Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.

5Department of Chemistry, MIT, Cambridge, MA 02139, USA.

8Department of Biological Engineering, MIT, Cambridge, MA 02139, USA.

9Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Cambridge, MA 02139, USA.

10Department of Physics, MIT, Cambridge, MA 02139, USA.

11Institute for Medical Engineering and Science, MIT, Cambridge, MA 02139, USA.

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John Kuriyan

1Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.

3Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

12Physical Biosciences and Materials Sciences Divisions, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.

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Jay T. Groves

1Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.

6Mechanobiology Institute, National University of Singapore, Singapore.

12Physical Biosciences and Materials Sciences Divisions, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.

13Berkeley Education Alliance for Research in Singapore, 1 Create Way, CREATE tower level 11, University Town, Singapore 138602.

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For correspondence: jtgroves@lbl.gov

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