Computational docking and solution x-ray scattering predict a membrane-interacting role for the histone domain of the Ras activator son of sevenless.
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 102 (2005-11-15), Heft 46, S. 16632-16637
Online
academicJournal
Zugriff:
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. [ABSTRACT FROM AUTHOR]
Titel: |
Computational docking and solution x-ray scattering predict a membrane-interacting role for the histone domain of the Ras activator son of sevenless.
|
---|---|
Autor/in / Beteiligte Person: | Sondermann, Holger ; Nagar, Bhushan ; Bar-Sagi, Dafna ; Kuriyan, John |
Link: | |
Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 102 (2005-11-15), Heft 46, S. 16632-16637 |
Veröffentlichung: | 2005 |
Medientyp: | academicJournal |
ISSN: | 0027-8424 (print) |
DOI: | 10.1073/pnas.0508315102 |
Schlagwort: |
|
Sonstiges: |
|