Cellular and Molecular Life Sciences

, Volume 74, Issue 17, pp 3205–3224 | Cite as

Functions of intrinsic disorder in transmembrane proteins

Multi-author Review

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

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

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Aarhus Institute of Advanced Studies (AIAS)Aarhus UniversityAarhusDenmark
  2. 2.Department of Molecular Biology and GeneticsAarhus UniversityAarhusDenmark
  3. 3.Interdisciplinary Nanoscience Center (iNANO)Aarhus UniversityAarhusDenmark
  4. 4.The Danish Research Institute of Translational Neuroscience (DANDRITE)AarhusDenmark
  5. 5.Structural Biology and NMR Laboratory and The Linderstrøm-Lang Centre for Protein Science, Department of BiologyUniversity of CopenhagenCopenhagenDenmark

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