Toll-like receptor 4 binding

Definition

Target type: molecularfunction

Binding to a Toll-like 4 protein, a pattern recognition receptor that binds bacterial lipopolysaccharide (LPS) to initiate an innate immune response. [GOC:BHF, PMID:18304834]

Toll-like receptor 4 (TLR4) is a transmembrane protein that plays a crucial role in the innate immune system by recognizing pathogen-associated molecular patterns (PAMPs) and initiating signaling pathways that lead to the production of pro-inflammatory cytokines and the activation of immune cells. The binding of TLR4 to its ligands, such as lipopolysaccharide (LPS) from Gram-negative bacteria, triggers a cascade of events that ultimately result in the activation of downstream signaling pathways. The molecular function of TLR4 binding can be summarized as follows:

1. **Ligand Recognition:** TLR4 recognizes and binds to a specific PAMP, such as LPS. This interaction is mediated by the extracellular domain of TLR4, which contains a horseshoe-shaped structure composed of leucine-rich repeats (LRRs).

2. **Conformational Changes:** Upon ligand binding, TLR4 undergoes conformational changes that lead to the recruitment of adaptor proteins, such as MyD88 and TRIF.

3. **Adaptor Protein Recruitment:** TLR4 interacts with MyD88 and TRIF through its cytoplasmic Toll/IL-1 receptor (TIR) domain. These adaptor proteins are essential for signal transduction and activation of downstream pathways.

4. **Signal Transduction:** MyD88 and TRIF recruit other signaling molecules, such as IRAK4 and TRAF6, which form a signaling complex. This complex activates downstream kinases, leading to the activation of transcription factors, such as NF-κB and IRF3.

5. **Cytokine Production:** The activated transcription factors translocate to the nucleus and induce the transcription of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6.

6. **Immune Cell Activation:** The cytokines produced by TLR4 signaling activate various immune cells, such as macrophages, neutrophils, and dendritic cells, to mount an immune response against the invading pathogen.

7. **Inflammation:** The activation of immune cells and the production of pro-inflammatory cytokines lead to inflammation, a protective response that helps to eliminate the pathogen.

In summary, the molecular function of TLR4 binding involves a complex series of events that begin with ligand recognition and culminate in the activation of immune cells and the induction of inflammation. This process is critical for host defense against pathogens.'
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Proteins (2)

Compounds (3)