TY - JOUR
T1 - Phosphorylation in protein-protein binding
T2 - Effect on stability and function
AU - Nishi, Hafumi
AU - Hashimoto, Kosuke
AU - Panchenko, Anna R.
N1 - Funding Information:
The authors thank Michael Galperin and Tom Madej for helpful discussions. K.H. was partially supported by a Research Fellowship from the Japan Society for the Promotion of Science. This work was supported by National Institutes of Health/Department of Health and Human Service (Intramural Research program of the National Library of Medicine).
PY - 2011/12/7
Y1 - 2011/12/7
N2 - Posttranslational modifications offer a dynamic way to regulate protein activity, subcellular localization, and stability. Here we estimate the effect of phosphorylation on protein binding and function for different types of complexes from human proteome. We find that phosphorylation sites tend to be located on binding interfaces in heterooligomeric and weak transient homooligomeric complexes. Analysis of molecular mechanisms of phosphorylation shows that phosphorylation may modulate the strength of interactions directly on interfaces and that binding hotspots tend to be phosphorylated in heterooligomers. Although the majority of complexes do not show significant estimated stability differences upon phosphorylation or dephosphorylation, for about one-third of all complexes it causes relatively large changes in binding energy. We discuss the cases where phosphorylation mediates the complex formation and regulates the function. We show that phosphorylation sites are more likely to be evolutionary conserved than other interfacial residues.
AB - Posttranslational modifications offer a dynamic way to regulate protein activity, subcellular localization, and stability. Here we estimate the effect of phosphorylation on protein binding and function for different types of complexes from human proteome. We find that phosphorylation sites tend to be located on binding interfaces in heterooligomeric and weak transient homooligomeric complexes. Analysis of molecular mechanisms of phosphorylation shows that phosphorylation may modulate the strength of interactions directly on interfaces and that binding hotspots tend to be phosphorylated in heterooligomers. Although the majority of complexes do not show significant estimated stability differences upon phosphorylation or dephosphorylation, for about one-third of all complexes it causes relatively large changes in binding energy. We discuss the cases where phosphorylation mediates the complex formation and regulates the function. We show that phosphorylation sites are more likely to be evolutionary conserved than other interfacial residues.
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U2 - 10.1016/j.str.2011.09.021
DO - 10.1016/j.str.2011.09.021
M3 - Article
C2 - 22153503
AN - SCOPUS:82955239916
VL - 19
SP - 1807
EP - 1815
JO - Structure with Folding & design
JF - Structure with Folding & design
SN - 0969-2126
IS - 12
ER -