title: Dynamic optimization of signal transduction via intrinsic disorder.
abstract: It is widely accepted that the inherent flexibility of intrinsically disordered proteins (IDPs) correlates with essential functions in the cell such as signaling. However, the mechanisms by which disorder dynamically facilitates and optimizes signal transduction remain unclear. In this study, we have used a computational protocol to evaluate the interplay between the intrinsic disorder of p27(kip1) and the collective motions of its binding partners, cyclin dependent kinase 2 (CDK2) and cyclin A (CA). We found that the synergy between intrinsic disorder of p27(kip1) and the essential collective motions of the CDK2-CA complex introduces a set of sequential steps to dynamically optimize signal transduction. Our observations indicate that optimized p27(kip1)-mediated signaling originates from a combination of adaptive folding, and the cooperativity between its residual disorder and the functional collective motions of the CDK2-CA complex.
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA. mef@ddt.biochem.umn.edu
authors.forename: L Michel
authors.initials: LM
authors.lastname: Espinoza-Fonseca
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D019925:Cyclin A / Q000737:chemistry / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000737:chemistry / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D025341:Principal Component Analysis; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D019925:Cyclin A; D011506:Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051357:Cyclin-Dependent Kinase 2