title: Dynamics on human Toll-like receptor 4 complexation to MD-2: the coreceptor stabilizing function.
abstract: The interaction between human Toll-like receptor 4 (hTLR4) and its coreceptor, myeloid differentiation factor 2 (MD-2), is important in Gram-negative bacteria lipopolysaccharide (LPS) recognition. In this process, MD-2 recognizes LPS and promotes the dimerization of the complex hTLR4-MD-2-LPS, triggering an intracellular immune signaling. In this study, we employed distinct computational methods to explore the dynamical properties of the hTLR4-MD-2 complex and investigated the implications of the coreceptor complexation to the structural biology of hTLR4. We characterized both global and local dynamics of free and MD-2 complexed hTLR4, in both (hTLR4-MD-2)1 and (hTLR4-MD-2)2 states. Both molecular dynamics and normal mode analysis reveled a stabilization of the terminal regions of hTLR4 upon complexation to MD-2. We are able to identify conserved important residues involved on the hTLR4-MD-2 interaction dynamics and disclose C-terminal motions that may be associated to the signaling process upon oligomerization.
authors.affiliation: Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, CP 15005, Porto Alegre, 91500-970, RS, Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: de Aguiar
authors.forename: Mauricio G S
authors.initials: MG
authors.lastname: Costa
authors.forename: Hugo
authors.initials: H
authors.lastname: Verli
mesh_terms: D001665:Binding Sites; D006801:Humans; D051218:Lymphocyte Antigen 96 / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D051197:Toll-Like Receptor 4 / Q000737:chemistry*
chemical_list: C495377:LY96 protein, human; D051218:Lymphocyte Antigen 96; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: TLR; innate immunity; molecular dynamics; normal mode; structural biology