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Cell Biochem Biophys (2016) 74:285296
DOI 10.1007/s12013-016-0752-7
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Web End = REVIEW PAPER
Interleukin-11: A Multifunctional Cytokine with Intrinsically Disordered Regions
Eugene A. Permyakov1 Vladimir N. Uversky1,2 Sergei E. Permyakov1
Received: 12 April 2016 / Accepted: 13 June 2016 / Published online: 22 June 2016 Springer Science+Business Media New York 2016
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 a-helices arranged in an upupdown
down conguration. 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-specic receptor IL-11Ra and a subsequent interaction of the complex with the transmembrane signal-transducing receptor GP130. Cytoplasmic domain of IL-11Ra 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 specic 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 119 lM, 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.
Keywords Interleukin Cytokines Intrinsically
disordered proteins Calcium-binding proteins Interleukin
receptors Hematopoietic system Tumor development
Introduction
Cytokines are small secreted proteins released by cells to modulate and control interactions and communications between cells. Being important players in cell signaling, cytokines include lymphokines (cytokines produced by lymphocytes), monokines (cytokines produced by monocytes), chemokines (cytokines with chemotactic activities), and interleukins (ILs, cytokines produced by leukocytes to affect behavior of other leukocytes; however, at present it is clear that...