Affinity of IDPs to their targets is modulated by ion-specific changes in kinetics and residual structure.

Abstract:

:Intrinsically disordered proteins (IDPs) are characterized by a lack of defined structure. Instead, they populate ensembles of rapidly interconverting conformations with marginal structural stabilities. Changes in solution conditions such as temperature and crowding agents consequently affect IDPs more than their folded counterparts. Here we reveal that the residual structure content of IDPs is modulated both by ionic strength and by the type of ions present in solution. We show that these ion-specific structural changes result in binding affinity shifts of up to sixfold, which happen through alteration of both association and dissociation rates. These effects follow the Hofmeister series, but unlike the well-established effects on the stability of folded proteins, they already occur at low, hypotonic concentrations of salt. We attribute this sensitivity to the marginal stability of IDPs, which could have physiological implications given the role of IDPs in signaling, the asymmetric ion profiles of different cellular compartments, and the role of ions in biology.

authors

Wicky BIM,Shammas SL,Clarke J

doi

10.1073/pnas.1705105114

subject

Has Abstract

pub_date

2017-09-12 00:00:00

pages

9882-9887

issue

37

eissn

0027-8424

issn

1091-6490

pii

1705105114

journal_volume

114

pub_type

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