Transient disorder: Calcineurin as an example

Intrinsically Disordered Proteins
Trevor P Creamer

Abstract

How intrinsically disordered proteins and regions evade degradation by cellular machinery evolved to recognize unfolded and misfolded chains remains a vexing question. One potential means by which this can occur is the disorder is transient in nature. That is, the disorder exists just long enough for it to be bound by a partner biomolecule and fold. A review of 30 y of studies of calmodulin's activation of calcineurin suggests that the regulatory domain of this vital phosphatase is a transiently disordered region. During activation, the regulatory domain progresses from a folded state, to disordered, followed by folding upon being bound by calmodulin. The transient disordered state of this domain is part of a critical intermediate state that facilitates the rapid binding of calmodulin. Building upon "fly-casting" as a means of facilitating partner binding, the mechanism by which calcineurin undergoes activation and subsequent deactivation could be considered "catch and release."

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Citations

Dec 11, 2019·Biomolecules·Vladimir N Uversky, Alexei V Finkelstein
Feb 7, 2016·The Journal of Biological Chemistry·Vladimir N Uversky
May 19, 2014·Intrinsically Disordered Proteins·Krishna D ReddyVladimir N Uversky
Nov 7, 2013·Intrinsically Disordered Proteins·Vladimir N Uversky
Sep 27, 2018·European Journal of Human Genetics : EJHG·Małgorzata RydzaniczRafał Płoski
Aug 30, 2020·Cell Communication and Signaling : CCS·Trevor P Creamer
May 18, 2016·Biochemistry·Erik C Cook, Trevor P Creamer
Aug 22, 2014·Biochemistry·Tori B DunlapTrevor P Creamer

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Methods Mentioned

BETA
ubiquitination
X-ray
circular dichroism

Software Mentioned

HXMS

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