Interleukin-11 Binds Specific EF-hand Proteins via Their Conserved Structural Motifs
Document Type
Article
Publication Date
2017
Keywords
cancer, intrinsic disorder, interleukin, EF-hand, S100 protein, neuronal calcium sensor, protein–protein interaction
Digital Object Identifier (DOI)
https://doi.org/10.1080/07391102.2015.1132392
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 ‘gray’ 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.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Journal of Biomolecular Structure and Dynamics, v. 35, issue 1, p. 78-91
Scholar Commons Citation
Kazakov, Alexei S.; Sokolov, Andrei S.; Vologzhannikova, Alisa A.; Permyakova, Maria E.; Khorn, Polina A.; Ismailov, Ramis G.; Denessiouk, Konstantin A.; Denesyuk, Alexander I.; Rastrygina, Victoria A.; Baksheeva, Viktoriia E.; Baksheeva, Evgeni Yu.; Zinchenko, Dmitry V.; Glazatov, Vladimir V.; Uversky, Vladimir N.; Mirzabekov, Tajib A.; Permyakov, Eugene A.; and Permyakov, Sergei E., "Interleukin-11 Binds Specific EF-hand Proteins via Their Conserved Structural Motifs" (2017). Molecular Medicine Faculty Publications. 309.
https://digitalcommons.usf.edu/mme_facpub/309
