The intracellular domain of TLR2 is capable of high‐affinity Zn binding: possible outcomes for the receptor activation

TL;DR

This study shows that the TLR2 receptor can bind zinc, which may help activate immune signals.

Contribution

The study reveals that TLR2's TIR domain binds zinc with high affinity, involving specific cysteine residues.

Findings

TLR2TIR binds zinc with nanomolar affinity via cysteine residues.

Cysteines C673 and C713 are essential for receptor activation.

Zinc may play a role in initiating signalosome assembly.

Abstract

Toll‐like receptors (TLRs) are important players in the innate immune system. Binding of pathogen‐related molecules to the extracellular domains of TLRs initiates signalosome assembly, a key event in signal transduction. Despite extensive research on individual receptor domains, the mechanism of signalosome assembly remains unclear. Recent evidence suggests that the intracellular TIR domain of TLR1 binds zinc ions, with cysteines playing a pivotal role in binding and receptor activation. This study explores the zinc‐binding ability of the TLR2 TIR domain (TLR2TIR). We found that TLR2TIR binds zinc with nanomolar affinity through its cysteine residues. Two of them, C673 and C713, are essential for receptor activation. These results suggest that zinc may be involved in the initiation of signalosome assembly.

Toll‐like receptors (TLRs) are important in the innate immune system. This study explores the zinc‐binding ability of the TLR2 TIR domain (TLR2TIR). We found that TLR2TIR binds zinc with nanomolar affinity through its cysteine residues. Two of them, C673 and C713, are vital for receptor activation, indicating that zinc may play a role in initiating signalosome assembly.

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