DOI: 10.1073/pnas.0508315102. Computational docking and solution x-ray scattering predict a membrane-interacting role for the histone domain of the Ras activator son of sevenless

Computational docking and solution x-ray scattering predict a membrane-interacting role for the histone domain of the Ras activator son of sevenless

10.1073/pnas.0508315102

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The Ras-specific nucleotide exchange factor son of sevenless (SOS) is a large, multidomain protein with complex regulation, including a Ras-dependent allosteric mechanism. The N-terminal segment of SOS, the histone domain, contains two histone folds, which is highly unusual for a cytoplasmic protein. Using a combination of computational docking, small-angle x-ray scattering, mutagenesis, and calorimetry, we show that the histone domain folds into the rest of SOS and docks onto a helical linker that connects the pleckstrin-homology (PH) and Dbl-homology (DH) domains of SOS to the catalytic domain. In this model, a positively charged surface region on the histone domain is positioned so as to provide a fourth potential anchorage site on the membrane for SOS in addition to the PH domain, the allosteric Ras molecule, and the C-terminal adapter-binding site. The histone domain in SOS interacts with the helical linker, using a region of the surface that in nucleosomes is involved in histone tetramerization. Adjacent surface elements on the histone domain that correspond to the DNA-binding surface of nucleosomes form the predicted interaction site with the membrane. The orientation and position of the histone domain in the SOS model implicates it as a potential mediator of membrane-dependent activation signals.

Bibliography

Sondermann, H., Nagar, B., Bar-Sagi, D., & Kuriyan, J. (2005). Computational docking and solution x-ray scattering predict a membrane-interacting role for the histone domain of the Ras activator son of sevenless. Proceedings of the National Academy of Sciences, 102(46), 16632â16637.

Authors 4

Holger Sondermann (first)
Bhushan Nagar (additional)
Dafna Bar-Sagi (additional)
John Kuriyan (additional)

References 29 Referenced 56

10.1126/science.1062023
10.2741/hall
10.1038/nrm1365
10.1038/28548
10.1016/S0092-8674(03)00149-1
10.1016/j.cell.2004.10.005
10.1128/MCB.18.2.880
10.1038/sj.onc.1201822
10.1128/MCB.18.2.771
10.1101/SQB.1994.059.01.021
10.1093/emboj/16.6.1351
Byrne, J. L., Paterson, H. F. & Marshall, C. J. (1996) Oncogene 13, 2055–2065.8950972 / Oncogene (1996)
10.1074/jbc.272.48.30340
10.1006/jmbi.1997.1041
10.1093/nar/23.14.2685
10.1016/j.str.2003.10.015
10.1038/38444
10.1093/nar/gkh354
10.1093/bioinformatics/btg371
10.1093/protein/14.2.105
10.1016/j.str.2004.11.014
10.1107/S0021889803012779
10.1107/S0021889892001663
10.1107/S0021889895007047
10.1074/jbc.M204423200
10.1017/S0033583503003871
10.1002/prot.340110407
Guinier A. & Fournet G. (1955) Small-Angle Scattering of X-Rays (Wiley New York).
10.1016/S1097-2765(00)00037-X

Dates

Type	When
Created	19 years, 9 months ago (Nov. 2, 2005, 8:25 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 2:12 p.m.)
Indexed	2 months, 1 week ago (June 10, 2025, 10:28 p.m.)
Issued	19 years, 9 months ago (Nov. 2, 2005)
Published	19 years, 9 months ago (Nov. 2, 2005)
Published Online	19 years, 9 months ago (Nov. 2, 2005)
Published Print	19 years, 9 months ago (Nov. 15, 2005)

Funders 0

None

BibTeX

@article{Sondermann_2005, title={Computational docking and solution x-ray scattering predict a membrane-interacting role for the histone domain of the Ras activator son of sevenless}, volume={102}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0508315102}, DOI={10.1073/pnas.0508315102}, number={46}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Sondermann, Holger and Nagar, Bhushan and Bar-Sagi, Dafna and Kuriyan, John}, year={2005}, month=nov, pages={16632–16637} }

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