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).

Erba, F., Di Paola, L., Di Venere, A., Mastrangelo, E., Cossu, F., Mei, G., et al. (2023). Head or tail? A molecular dynamics approach to the complex structure of TNF-associated factor TRAF2. BIOMOLECULAR CONCEPTS, 14(1) [10.1515/bmc-2022-0031].

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

Erba F.
Membro del Collaboration Group
;
Di Venere A.
Membro del Collaboration Group
;
Mei G.
Conceptualization
;
Minicozzi V.
Conceptualization
2023-01-01

Abstract

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
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore FIS/07
English
molecular dynamics
protein contact networks
quaternary interaction
TRAFs
Erba, F., Di Paola, L., Di Venere, A., Mastrangelo, E., Cossu, F., Mei, G., et al. (2023). Head or tail? A molecular dynamics approach to the complex structure of TNF-associated factor TRAF2. BIOMOLECULAR CONCEPTS, 14(1) [10.1515/bmc-2022-0031].
Erba, F; Di Paola, L; Di Venere, A; Mastrangelo, E; Cossu, F; Mei, G; Minicozzi, V
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/347468
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 2
  • ???jsp.display-item.citation.isi??? ND
social impact