Jump to main content
Jump to site search

Issue 14, 2014
Previous Article Next Article

The binding mechanisms of intrinsically disordered proteins

Author affiliations

Abstract

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) of proteins are very common and instrumental for cellular signaling. Recently, a number of studies have investigated the kinetic binding mechanisms of IDPs and IDRs. These results allow us to draw conclusions about the energy landscape for the coupled binding and folding of disordered proteins. The association rate constants of IDPs cover a wide range (105–109 M−1 s−1) and are largely governed by long-range charge–charge interactions, similarly to interactions between well-folded proteins. Off-rate constants also differ significantly among IDPs (with half-lives of up to several minutes) but are usually around 0.1–1000 s−1, allowing for rapid dissociation of complexes. Likewise, affinities span from pM to μM suggesting that the low-affinity high-specificity concept for IDPs is not straightforward. Overall, it appears that binding precedes global folding although secondary structure elements such as helices may form before the protein–protein interaction. Short IDPs bind in apparent two-state reactions whereas larger IDPs often display complex multi-step binding reactions. While the two extreme cases of two-step binding (conformational selection and induced fit) or their combination into a square mechanism is an attractive model in theory, it is too simplistic in practice. Experiment and simulation suggest a more complex energy landscape in which IDPs bind targets through a combination of conformational selection before binding (e.g., secondary structure formation) and induced fit after binding (global folding and formation of short-range intermolecular interactions).

Graphical abstract: The binding mechanisms of intrinsically disordered proteins

Back to tab navigation

Additions and corrections

Publication details

The article was received on 07 Oct 2013, accepted on 12 Nov 2013 and first published on 06 Dec 2013


Article type: Perspective
DOI: 10.1039/C3CP54226B
Citation: Phys. Chem. Chem. Phys., 2014,16, 6323-6331
  •   Request permissions

    The binding mechanisms of intrinsically disordered proteins

    J. Dogan, S. Gianni and P. Jemth, Phys. Chem. Chem. Phys., 2014, 16, 6323
    DOI: 10.1039/C3CP54226B

Search articles by author

Spotlight

Advertisements