Interleukin-11 binds specific EF-hand proteins via their conserved structural motifs

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Kazakov AS, Sokolov AS, Vologzhannikova AA, Permyakova ME, Khorn PA, Ismailov RG, Denessiouk KA, Denesyuk AI, Rastrygina VA, Baksheeva VE, Zernii EY, Zinchenko DV, Glazatov VV, Uversky VN, Mirzabekov TA, Permyakov EA, Permyakov SE
Publisher: Taylor & Francis
Publication year: 2016
Journal: Journal of Biomolecular Structure and Dynamics
Journal acronym: J Biomol Struct Dyn
Start page: 1
End page: 14
eISSN: 1538-0254


Abstract

Interleukin-11 (IL-11) is a hematopoietic cytokine engaged in numerous biological processes and validated as a target for treatment of various cancers. IL-11 contains intrinsically disordered regions that might recognize multiple targets. Recently we found that aside from IL-11RA and gp130 receptors IL-11 interacts with calcium sensor protein S100P. Strict calcium dependence of this interaction suggests a possibility of IL-11 interaction with other calcium sensor proteins. Here we probed specificity of IL-11 to calcium-binding proteins of various types: calcium sensors of the EF-hand family (calmodulin, S100B and neuronal calcium sensors: recoverin, NCS-1, GCAP-1, GCAP-2), calcium buffers of the EF-hand family (S100G, oncomodulin), and a non-EF-hand calcium buffer (α-lactalbumin). A specific subset of the calcium sensor proteins (calmodulin, S100B, NCS-1, GCAP-1/2) exhibits metal-dependent binding of IL-11 with dissociation constants of 1-19 μM. These proteins share several amino acid residues belonging to conservative structural motifs of the EF-hand proteins, 'black' and 'grey' clusters. Replacements of the respective S100P residues by alanine drastically decrease its affinity to IL-11, suggesting their involvement into the association process. Secondary structure and accessibility of the hinge region of the EF-hand proteins studied are predicted to control specificity and selectivity of their binding to IL-11. The IL-11 interaction with the EF-hand proteins is expected to occur under numerous pathological conditions, accompanied by disintegration of plasma membrane and efflux of cellular components into the extracellular milieu.


Keywords

cancer; intrinsic disorder; interleukin; EF-hand;

Last updated on 2019-21-07 at 05:44