Intrinsically disordered cytoplasmic domains of two cytokine receptors mediate conserved interactions with membranes

Haxholm, Gitte W, Nikolajsen, Louise F, Olsen, Johan G, Fredsted, Jacob, Larsen, Flemming H, Goffin, Vincent, Pedersen, Stine F, Brooks, Andrew J, Waters, Michael J and Kragelund, Birthe B (2015) Intrinsically disordered cytoplasmic domains of two cytokine receptors mediate conserved interactions with membranes. Biochemical Journal, 468 3: 495-506. doi:10.1042/BJ20141243


Author Haxholm, Gitte W
Nikolajsen, Louise F
Olsen, Johan G
Fredsted, Jacob
Larsen, Flemming H
Goffin, Vincent
Pedersen, Stine F
Brooks, Andrew J
Waters, Michael J
Kragelund, Birthe B
Title Intrinsically disordered cytoplasmic domains of two cytokine receptors mediate conserved interactions with membranes
Journal name Biochemical Journal   Check publisher's open access policy
ISSN 1470-8728
0264-6021
Publication date 2015-06-15
Year available 2015
Sub-type Article (original research)
DOI 10.1042/BJ20141243
Volume 468
Issue 3
Start page 495
End page 506
Total pages 12
Place of publication London, United Kingdom
Publisher Portland Press Ltd
Collection year 2016
Language eng
Abstract Class 1 cytokine receptors regulate essential biological processes through complex intracellular signalling networks. However, the structural platform for understanding their functions is currently incomplete as structure–function studies of the intracellular domains (ICDs) are critically lacking. The present study provides the first comprehensive structural characterization of any cytokine receptor ICD and demonstrates that the human prolactin (PRL) receptor (PRLR) and growth hormone receptor (GHR) ICDs are intrinsically disordered throughout their entire lengths. We show that they interact specifically with hallmark lipids of the inner plasma membrane leaflet through conserved motifs resembling immuno receptor tyrosine-based activation motifs (ITAMs). However, contrary to the observations made for ITAMs, lipid association of the PRLR and GHR ICDs was shown to be unaccompanied by changes in transient secondary structure and independent of tyrosine phosphorylation. The results of the present study provide a new structural platform for studying class 1 cytokine receptors and may implicate the membrane as an active component regulating intracellular signalling.
Keyword Growth hormone receptor
Immuno t-cell receptor activation motifs
Intrinsically disordered protein
Membrane interaction
Prolactin receptor
Signalling
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
UQ Diamantina Institute Publications
 
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