Network of interactions between the tumor necrosis factor superfamily members and small S100 proteins
- 1Institute for Biological Instrumentation of the Russian Academy of Sciences, Moscow Region, Russia
- 2Department of Molecular Medicine and USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America
Abstract
Tumor Necrosis Factor Superfamily (TNFSF) comprises 20 members of membrane/soluble signaling proteins regulating cell survival, cell proliferation/differentiation, and innate/adaptive immunity. Targeting signaling of TNFSF members is used clinically to treat several autoimmune and oncological diseases, and bone loss. They and their cognate receptors are in clinical trials as targets for treatment of autoimmune, inflammatory, oncological and other diseases. Recently, some representatives of S100 family of pleiotropic calcium-binding proteins were shown to interact with TNFSF members TNF and TRAIL, thereby suppressing their activity. In this work, we explored selectivity of interactions between soluble forms of 13 TNFSF members and 21 non-fused S100 proteins using surface plasmon resonance spectroscopy. A total of 27 interactions were found between CD70, CD30L, 4−1BBL, TWEAK, APRIL, LIGHT, VEGI and AITRL and Ca2+-loaded forms of S100A1/A2/A4/A5/A6/A12/A16/B/P proteins, with equilibrium dissociation constants from 2 nM to 24 μM. Removal of calcium leads to disruption of the interactions. Molecular docking indicates presence of well-conserved binding sites of the both interaction partners. Mutagenesis of S100P evidences involvement of its ‘hinge’ region in binding of CD30L, VEGI and AITRL, as well as F89 residue in VEGI recognition. The revealed network of interactions is potentially important for regulation of the cellular communication mediated by TNFSF/S100 proteins, which could be exploited for targeted therapy of socially significant diseases.
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BibTeX
@article{rastrygina2026network,
title = {{Network of interactions between the tumor necrosis factor superfamily members and small S100 proteins}},
author = {Victoria A. Rastrygina and Evgenia I. Deryusheva and Alexey S. Kazakov and Andrey S. Sokolov and Maria E. Permyakova and Ekaterina A. Litus and Vladimir N. Uversky and Eugene A. Permyakov and Sergei E. Permyakov},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0341400},
url = {https://doi.org/10.1371/journal.pone.0341400},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Network of interactions between the tumor necrosis factor superfamily members and small S100 proteins
AU - Victoria A. Rastrygina
AU - Evgenia I. Deryusheva
AU - Alexey S. Kazakov
AU - Andrey S. Sokolov
AU - Maria E. Permyakova
AU - Ekaterina A. Litus
AU - Vladimir N. Uversky
AU - Eugene A. Permyakov
AU - Sergei E. Permyakov
PY - 2026
DA - 2026/09/29
JO - PLOS One
DO - 10.1371/journal.pone.0341400
UR - https://doi.org/10.1371/journal.pone.0341400
AB - Tumor Necrosis Factor Superfamily (TNFSF) comprises 20 members of membrane/soluble signaling proteins regulating cell survival, cell proliferation/differentiation, and innate/adaptive immunity. Targeting signaling of TNFSF members is used clinically to treat several autoimmune and oncological diseases, and bone loss. They and their cognate receptors are in clinical trials as targets for treatment of autoimmune, inflammatory, oncological and other diseases. Recently, some representatives of S100 family of pleiotropic calcium-binding proteins were shown to interact with TNFSF members TNF and TRAIL, thereby suppressing their activity. In this work, we explored selectivity of interactions between soluble forms of 13 TNFSF members and 21 non-fused S100 proteins using surface plasmon resonance spectroscopy. A total of 27 interactions were found between CD70, CD30L, 4−1BBL, TWEAK, APRIL, LIGHT, VEGI and AITRL and Ca2+-loaded forms of S100A1/A2/A4/A5/A6/A12/A16/B/P proteins, with equilibrium dissociation constants from 2 nM to 24 μM. Removal of calcium leads to disruption of the interactions. Molecular docking indicates presence of well-conserved binding sites of the both interaction partners. Mutagenesis of S100P evidences involvement of its ‘hinge’ region in binding of CD30L, VEGI and AITRL, as well as F89 residue in VEGI recognition. The revealed network of interactions is potentially important for regulation of the cellular communication mediated by TNFSF/S100 proteins, which could be exploited for targeted therapy of socially significant diseases.
SN - 1932-6203
ER -