Open AccessInterface Analysis of the Complex between ERK2 and PTP-SL
Author(s) -
Mihaela C. Balasu,
Laurentiu N. Spiridon,
Simona Miron,
Constantin T. Craescu,
Axel J. Scheidig,
Andrei-José Petrescu,
Stefan E. Szedlacsek
Publication year - 2009
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0005432
Subject(s) - isothermal titration calorimetry , effector , phosphatase , regulator , complex formation , docking (animal) , chemistry , protein–protein interaction , biophysics , computational biology , stereochemistry , biology , biochemistry , enzyme , medicine , inorganic chemistry , nursing , gene
The activity of ERK2, an essential component of MAP-kinase pathway, is under the strict control of various effector proteins. Despite numerous efforts, no crystal structure of ERK2 complexed with such partners has been obtained so far. PTP-SL is a major regulator of ERK2 activity. To investigate the ERK2–PTP-SL complex we used a combined method based on cross-linking, MALDI-TOF analysis, isothermal titration calorimetry, molecular modeling and docking. Hence, new insights into the stoichiometry, thermodynamics and interacting regions of the complex are obtained and a structural model of ERK2-PTP-SL complex in a state consistent with PTP-SL phosphatase activity is developed incorporating all the experimental constraints available at hand to date. According to this model, part of the N-terminal region of PTP-SL has propensity for intrinsic disorder and becomes structured within the complex with ERK2. The proposed model accounts for the structural basis of several experimental findings such as the complex-dissociating effect of ATP, or PTP-SL blocking effect on the ERK2 export to the nucleus. A general observation emerging from this model is that regions involved in substrate binding in PTP-SL and ERK2, respectively are interacting within the interface of the complex.