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Review
. 2018 Apr 30:5:39.
doi: 10.3389/fmolb.2018.00039. eCollection 2018.

Intramolecular Fuzzy Interactions Involving Intrinsically Disordered Domains

Miguel Arbesú  1 , Guillermo Iruela  1 , Héctor Fuentes  1 , João M C Teixeira  1 , Miquel Pons  1
Affiliations
Review

Intramolecular Fuzzy Interactions Involving Intrinsically Disordered Domains

Miguel Arbesú et al. Front Mol Biosci. .

Abstract

Structural disorder is an essential ingredient for function in many proteins and protein complexes. Fuzzy complexes describe the many instances where disorder is maintained as a critical element of protein interactions. In this minireview we discuss how intramolecular fuzzy interactions function in signaling complexes. Focussing on the Src family of kinases, we argue that the intrinsically disordered domains that are unique for each of the family members and display a clear fingerprint of long range interactions in Src, might have critical roles as functional sensor or effectors and mediate allosteric communication via fuzzy interactions.

Keywords: Src family kinases; allostery; fuzzy complexes; fuzzy domains; intrinsically disordered proteins; paramagnetic relaxation enhancement.

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Figures

Figure 1
Figure 1
IDRs and information transfer. IDRs can act as linkers, effectors, or sensors. (A) In the linker case, the IDR transmits the information between folded sensor and an effector domains. (B) The IDR can become an effector, e.g., by folding as a response to a stimulus. (C) A fuzzy complex, like in Src, can act as a sensor with the folded SH3 domain (in black) taking the role of the linker.
Figure 2
Figure 2
Switches and rheostats in Src Family Kinases. The conserved SH3-SH2-SH1 multidomain cassette implements an on/off switch based on the interaction between the phosphorylated C-terminal tail and the SH2 domain, as well as interactions involving the SH3 domain. The intrinsically disordered N-terminal region forms a fuzzy complex with the SH3 domain and enables a program that could direct different qualitative and quantitative outputs depending on the environment. Thus, the IDRs can function as selective rheostats. Within the Src Family of Kinases, the high homology among of the SH3-SH2-SH1 cassette contrasts with the uniqueness of the disordered N-terminal regions, suggesting a modular architecture in which specific responses are programmed in the IDR.
See this image and copyright information in PMC

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