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Cell Mol Life Sci. 2017 Sep;74(17):3205-3224. doi: 10.1007/s00018-017-2562-5. Epub 2017 Jun 10.

Functions of intrinsic disorder in transmembrane proteins.

Author information

1
Aarhus Institute of Advanced Studies (AIAS), Aarhus University, Aarhus, Denmark. magnus@aias.au.dk.
2
Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark. magnus@aias.au.dk.
3
Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, Denmark. magnus@aias.au.dk.
4
The Danish Research Institute of Translational Neuroscience (DANDRITE), Aarhus, Denmark. magnus@aias.au.dk.
5
Structural Biology and NMR Laboratory and The Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Copenhagen, Denmark.

Abstract

Intrinsic disorder is common in integral membrane proteins, particularly in the intracellular domains. Despite this observation, these domains are not always recognized as being disordered. In this review, we will discuss the biological functions of intrinsically disordered regions of membrane proteins, and address why the flexibility afforded by disorder is mechanistically important. Intrinsically disordered regions are present in many common classes of membrane proteins including ion channels and transporters; G-protein coupled receptors (GPCRs), receptor tyrosine kinases and cytokine receptors. The functions of the disordered regions are many and varied. We will discuss selected examples including: (1) Organization of receptors, kinases, phosphatases and second messenger sources into signaling complexes. (2) Modulation of the membrane-embedded domain function by ball-and-chain like mechanisms. (3) Trafficking of membrane proteins. (4) Transient membrane associations. (5) Post-translational modifications most notably phosphorylation and (6) disorder-linked isoform dependent function. We finish the review by discussing the future challenges facing the membrane protein community regarding protein disorder.

KEYWORDS:

Ball-and-chain inhibition; Intrinsically disordered protein; Lipid interaction domain; Membrane protein; Receptor associated signalling complex

PMID:
28601983
DOI:
10.1007/s00018-017-2562-5
[Indexed for MEDLINE]

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