Head or tail? A molecular dynamics approach to the complex structure of TNF-associated factor TRAF2.

Autor:	Erba F; Department of Clinical Science and Translational Medicine, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy., Di Paola L; Unit of Chemical-Physics Fundamentals in Chemical Engineering, Department of Engineering, University Campus Bio-Medico of Rome, Via Álvaro del Portillo 21, 00128 Rome, Italy., Di Venere A; Department of Experimental Medicine, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy., Mastrangelo E; National Research Council (IBF-CNR) Milan Unit, Institute of Biophysics, Via Celoria 26, 20133 Milan, Italy., Cossu F; National Research Council (IBF-CNR) Milan Unit, Institute of Biophysics, Via Celoria 26, 20133 Milan, Italy., Mei G; Department of Experimental Medicine, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy., Minicozzi V; Department of Physics and INFN, Tor Vergata University of Rome, Via Della Ricerca Scientifica 1, 00133 Rome, Italy.
Jazyk:	angličtina
Zdroj:	Biomolecular concepts [Biomol Concepts] 2023 Jun 28; Vol. 14 (1). Date of Electronic Publication: 2023 Jun 28 (Print Publication: 2023).
DOI:	10.1515/bmc-2022-0031
Abstrakt:	Tumor necrosis factor receptor-associated factor proteins (TRAFs) are trimeric proteins that play a fundamental role in signaling, acting as intermediaries between the tumor necrosis factor (TNF) receptors and the proteins that transmit the downstream signal. The monomeric subunits of all the TRAF family members share a common tridimensional structure: a C-terminal globular domain and a long coiled-coil tail characterizing the N-terminal section. In this study, the dependence of the TRAF2 dynamics on the length of its tail was analyzed in silico . In particular, we used the available crystallographic structure of a C-terminal fragment of TRAF2 (168 out of 501 a.a.), TRAF2-C, and that of a longer construct, addressed as TRAF2-plus, that we have re-constructed using the AlphaFold2 code. The results indicate that the longer N-terminal tail of TRAF2-plus has a strong influence on the dynamics of the globular regions in the protein C-terminal head. In fact, the quaternary interactions among the TRAF2-C subunits change asymmetrically in time, while the movements of TRAF2-plus monomers are rather limited and more ordered than those of the shorter construct. Such findings shed a new light on the dynamics of TRAF subunits and on the protein mechanism in vivo , since TRAF monomer-trimer equilibrium is crucial for several reasons (receptor recognition, membrane binding, hetero-oligomerization). (© 2023 the author(s), published by De Gruyter.)
Databáze:	MEDLINE
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