Interleukin-11: A Multifunctional Cytokine with Intrinsically Disordered Regions

Cell Biochemistry and Biophysics volume 74, pages 285–296 (2016)Cite this article

Abstract

Cytokine interleukin-11 (IL-11) is a multifunctional protein with diverse roles in the normal cell signaling and in various pathologies. The structure of IL-11 is characterized by a four-helix bundle motif comprising two pairs of antiparallel α-helices arranged in an up–up–down–down configuration. Evaluation of the intrinsic disorder predisposition of human IL-11 by several computational tools clearly shows that this protein is predicted to have functional disordered regions potentially involved in interaction with natural binding partners. Signaling by IL-11 proceeds via an interaction of the protein with its membrane-specific receptor IL-11Rα and a subsequent interaction of the complex with the transmembrane signal-transducing receptor GP130. Cytoplasmic domain of IL-11Rα is predicted to be very disordered, and noticeable amount of disorder is present even in the large extracellular domain of the protein. GP130 is also predicted to have long disordered region that is located at the C-terminal of the protein and is expected to have several disorder-based binding sites. It shows that intrinsic disorder might play an important role in functioning of this signaling machine. A specific subset of the calcium sensor proteins (calmodulin, S100P, S100B, NCS-1, GCAP-1/2) exhibits metal-dependent binding of IL-11 with dissociation constants in a range of 1–19 μM, and the structural features of their hinge regions likely ensure selectivity and calcium sensitivity of IL-11 binding to the EF-hand proteins studied. IL-11 exhibits multiple effects on hematopoietic and non-hematopoietic systems. It plays a major role in orchestrating complex processes of tumor development and progression.

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Acknowledgments

This work was supported by a grant to E. A. P. from the Ministry of Education and Science of the Russian Federation (No. 14.607.21.0097, RFMEFI60714X0097).

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Affiliations

  1. Institute for Biological Instrumentation, Russian Academy of Sciences, Pushchino, Moscow, Russia, 142290

    Eugene A. Permyakov, Vladimir N. Uversky & Sergei E. Permyakov

  2. Department of Molecular Medicine, USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA

    Vladimir N. Uversky

Authors
  1. Eugene A. Permyakov
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  2. Vladimir N. Uversky
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  3. Sergei E. Permyakov
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Correspondence to Eugene A. Permyakov.

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Permyakov, E.A., Uversky, V.N. & Permyakov, S.E. Interleukin-11: A Multifunctional Cytokine with Intrinsically Disordered Regions. Cell Biochem Biophys 74, 285–296 (2016). https://doi.org/10.1007/s12013-016-0752-7

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Keywords

  • Interleukin
  • Cytokines
  • Intrinsically disordered proteins
  • Calcium-binding proteins
  • Interleukin receptors
  • Hematopoietic system
  • Tumor development