Homology modeling of human Toll-like receptors TLR7, 8, and 9 ligand-binding domains

AUTOR(ES)

Wei, Tiandi

FONTE

Wiley Subscription Services

RESUMO

Toll-like receptors (TLRs) play a key role in the innate immune system. The TLR7, 8, and 9 compose a family of intracellularly localized TLRs that signal in response to pathogen-derived nucleic acids. So far, there are no crystallographic structures for TLR7, 8, and 9. For this reason, their ligand-binding mechanisms are poorly understood. To enable first predictions of the receptor–ligand interaction sites, we developed three-dimensional structures for the leucine-rich repeat ectodomains of human TLR7, 8, and 9 based on homology modeling. To achieve a high sequence similarity between targets and templates, structural segments from all known TLR ectodomain structures (human TLR1/2/3/4 and mouse TLR3/4) were used as candidate templates for the modeling. The resulting models support previously reported essential ligand-binding residues. They also provide a basis to identify three potential receptor dimerization mechanisms. Additionally, potential ligand-binding residues are identified using combined procedures. We suggest further investigations of these residues through mutation experiments. Our modeling approach can be extended to other members of the TLR family or other repetitive proteins.

Documentos Relacionados

• The molecular structure of the Toll-like receptor 3 ligand-binding domain
• Haplotype variation in bovine Toll-like receptor 4 and computational prediction of a positively selected ligand-binding domain
• Toll-like Receptors of the Ascidian Ciona intestinalis: PROTOTYPES WITH HYBRID FUNCTIONALITIES OF VERTEBRATE TOLL-LIKE RECEPTORS
• Toll-like receptor 4 (TLR4) na modulação da imunidade do tipo 2.
• The evolution of vertebrate Toll-like receptors