Evaluating the Topological Features of Monomeric and Trimeric TRAF2-C: A Multi-Disciplinary Approach
Fulvio Erba, Daniela Russo, Velia Minicozzi, Luisa Di Paola, Sylvain Prevost, Anastasia De Luca, Giampiero Mei, Almerinda Di Venere
TL;DR
This study explores how the TRAF2-C protein switches between monomeric and trimeric forms, revealing structural changes that could influence cell signaling and disease.
Contribution
The study provides new insights into TRAF2-C's structural dynamics using a combination of experimental and computational methods.
Findings
TRAF2-C dissociates into monomers at low concentrations and favors trimerization at higher concentrations.
Dissociation reduces α-helical content but preserves the overall protein fold.
Molecular dynamics and contact network analysis identify key residues and bonds stabilizing TRAF2-C oligomers.
Abstract
This study investigates the structural dynamics of the TRAF2 C-terminal domain (TRAF2-C), a key adaptor protein in TNF receptor signaling. TRAF2 usually forms trimers, but its ability to dissociate into monomers is critical for regulating apoptosis, inflammation, and cell survival. Using Fluorescence Fluctuation Spectroscopy, dynamic light scattering, circular dichroism, and Small Angle Neutron Scattering, we analyzed TRAF2-C over a wide concentration range. At nanomolar levels, the protein dissociates easily, with trimers representing only a minor fraction, while micromolar concentrations strongly favor trimerization. Dissociation also reduces α-helical content without disrupting the overall fold. Molecular dynamics simulations and protein contact network analysis support this analysis, identifying interfacial residues and hydrogen bonds as key factors stabilizing oligomers and…
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Taxonomy
TopicsNF-κB Signaling Pathways · Melanoma and MAPK Pathways · Protein Tyrosine Phosphatases