Toll-like receptor 4 pathway evolutionary trajectory and functional emergence.

ABSTRACT:

Introduction

Toll-like receptors 4 (TLR4) recognize lipopolysaccharides (LPS) from bacteria as their conventional ligands and undergo downstream signaling to produce cytokines. They mediate the signaling either by the TIRAP-MyD88 complex or by the TRAM-TRIF complex. The MyD88 pathway is common to all other TLRs, whereas the TRAM-TRIF complex is largely exclusive to TLR4. Here we study the TIR domain of TRAM and TRIF ortholog proteins that are crucial for downstream signaling. Our previous work on pan-genome-wide survey, indicates Callorhincus milli to be the ancestral organism with both TRAM and TRIF proteins.

Methods

To gain a deeper insight into the protein function and to compare them with Homo sapiens adaptor proteins, we modeled the docking of the TRAM-TRI

SUBMITTER: Verma S 

PROVIDER: S-EPMC11788365 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature