Oligomerization analysis as a tool to elucidate the mechanism of EBV latent membrane protein 1 inhibition by pentamidine

Exploring the trimerization process of a transmembrane helix with an ionizable residue by molecular dynamics simulations: a case study of transmembrane domain 5 of LMP-1

“…This is highly consistent with our previous NMR study in which the p K a of D150 in TMD5 in DPC micelles was 7.4. 29 When the reaction coordinate increased to 21.15 Å or 26.15 Å, D150 not only interacted with the neighboring monomers but was also influenced by the lipids. The relative position of D150 in the bilayer along the z -axis was measured to reflect the interactions of D150 with lipids (Fig.…”

“…25 Further studies showed that truncated TMD5 strongly self-associates by forming a homotrimeric complex in the membrane. 25–29 A series of disruptors targeting TMD5 lateral protein–protein interactions (PPIs) by directly interacting with D150 inhibited LMP-1 oligomerization. 26–28 Further investigation showed that the D150-protonated TMD5 trimer was stable, whereas unprotonated D150 created bending in the helices that distorted the trimeric structure.…”

Neurotrophin signaling is modulated by specific transmembrane domain interactions

“…To identify the oligomer size of the complex, we measured the cross-correlated relaxation rates of p75-TM-C257A signals (Figure S1). According to the recent work, the NMR-derived hydrodynamic radii of TM domains in DPC micelles can be used to distinguish the various oligomeric forms of the proteins (37). Here we observed the rotational correlation time (and hydrodynamic radius) of a p75-TM-C257A monomer at 45 °C to be 10.2±0.4 ns (2.61 nm), a p75-TM-C257A homodimer to be 13.1±0.6 ns (2.85 nm) and the heterocomplex to be 12.7±0.8 ns (2.82 nm).…”

“…To identify the oligomer size of the complex, we measured the cross-correlated relaxation rates of p75-TM-C257A signals (Figure S1). According to the recent work, the NMR-derived hydrodynamic radii of TM domains in DPC micelles can be used to distinguish the various oligomeric forms of the proteins (37) With the increase of TrkA concentration, the percentage of p75 homodimer decreased while that of p75/TrkA heterodimer increased (Figure 2C). This implies that homoand heterodimerization of p75-TM are the competing processes.…”

Interaction between the transmembrane domains of neurotrophin receptors p75 and TrkA mediates their reciprocal activation

“…To identify the oligomer size of the complex, we measured the crosscorrelated relaxation rates of p75-TM-C257A signals (Figure S1). According to the recent work, the NMR-derived hydrodynamic radii of TM domains in DPC micelles can be used to distinguish the various oligomeric forms of the proteins (37) 2C). This implies that homoand heterodimerization of p75-TM are the competing processes.…”