| Title: | Protein-protein interaction affinity plays a crucial role in controlling the Sho1p-mediated signal transduction pathway in yeast |
| Author(s): | Marles JA; Dahesh S; Haynes J; Andrews BJ; Davidson AR; |
| Address: | "Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada" |
| DOI: | 10.1016/j.molcel.2004.05.024 |
| ISSN/ISBN: | 1097-2765 (Print) 1097-2765 (Linking) |
| Abstract: | "Protein-protein interactions are required for most cellular functions, yet little is known about the relationship between protein-protein interaction affinity and biological activity. To investigate this issue, we engineered a series of mutants that incrementally reduced the affinity of the yeast Sho1p SH3 domain for its in vivo target, the MAP kinase kinase Pbs2p. We demonstrate a strong linear correlation between the binding energy of these mutants and quantitative in vivo outputs from the HOG high-osmolarity response pathway controlled by Sho1p. In addition, we find that reduction in binding affinity for the correct target within this pathway causes a proportional increase in misactivation of the related mating pheromone response pathway and that strong binding affinity alone does not guarantee efficient biological activity. Our experiments also indicate that a second binding surface on the Sho1p SH3 domain is required for its proper in vivo function" |
| Keywords: | Amino Acid Sequence Binding Sites Conserved Sequence *MAP Kinase Signaling System Membrane Proteins/chemistry/genetics/*metabolism Mitogen-Activated Protein Kinases/metabolism Molecular Sequence Data Mutation Saccharomyces cerevisiae/*metabolism Saccharom; |
| Notes: | "MedlineMarles, Jennifer A Dahesh, Samira Haynes, Jennifer Andrews, Brenda J Davidson, Alan R eng Research Support, Non-U.S. Gov't 2004/06/18 Mol Cell. 2004 Jun 18; 14(6):813-23. doi: 10.1016/j.molcel.2004.05.024" |
