The robustness of proofreading to crowding-induced pseudo-processivity in the MAPK pathway
File(s)
Accepted version
Author(s)
Ouldridge, TE
Wolde, PRT
Type
Journal Article
Abstract
© 2014 Biophysical Society.Double phosphorylation of protein kinases is a common feature of signaling cascades. This motif may reduce cross-talk between signaling pathways because the second phosphorylation site allows for proofreading, especially when phosphorylation is distributive rather than processive. Recent studies suggest that phosphorylation can be pseudo-processive in the crowded cellular environment, since rebinding after the first phosphorylation is enhanced by slow diffusion. Here, we use a simple model with unsaturated reactants to show that specificity for one substrate over another drops as rebinding increases and pseudo-processive behavior becomes possible. However, this loss of specificity with increased rebinding is typically also observed if two distinct enzyme species are required for phosphorylation, i.e., when the system is necessarily distributive. Thus the loss of specificity is due to an intrinsic reduction in selectivity with increased rebinding, which benefits inefficient reactions, rather than pseudo-processivity itself. We also show that proofreading can remain effective when the intended signaling pathway exhibits high levels of rebinding-induced pseudo-processivity, unlike other proposed advantages of the dual phosphorylation motif.
Date Issued
2014-11-18
ISSN
0006-3495
Publisher
Biopysical Society
Start Page
2425
End Page
2435
Journal / Book Title
Biophysical Journal
Volume
107
Issue
10
Copyright Statement
© 2014 by the Biophysical Society. Published by Elsevier Inc. All rights reserved. NOTICE: this is the author’s version of a work that was accepted for publication in Biophysical Journal. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in BIOPHYSICAL JOURNAL, Vol.: 107, Issue: 10, (2014) DOI: 10.1016/j.bpj.2014.10.020
Description
08.01.12 KB. Ok to add accepted version to spiral, no embargo. Could not find set statement, used Elsiever
Identifier
http://arxiv.org/abs/1407.1499v2
Notes
To appear in Biohys. J