Are different stoichiometries feasible for complexes between lymphotoxin-alpha and tumor necrosis factor receptor 1?

ABSTRACT:

Background

Tumor necrosis factors, TNF and lymphotoxin-α (LT), are cytokines that bind to two receptors, TNFR1 and TNFR2 (TNF-receptor 1 and 2) to trigger their signaling cascades. The exact mechanism of ligand-induced receptor activation is still unclear. It is generally assumed that three receptors bind to the homotrimeric ligand to trigger a signaling event. Recent evidence, though, has raised doubts if the ligand:receptor stoichiometry should indeed be 3:3 for ligand-induced cellular response. We used molecular dynamics simulations, elastic network models, as well as MM/PBSA to analyze this question.

Results

Applying MM/PBSA methodology to different stoichiometric complexes of human LT-(TNFR1)n=1,2,3 the free energy of binding in these complexes has been estimated by sin

SUBMITTER: Mascarenhas NM 

PROVIDER: S-EPMC3412742 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature