Supramolecularity creates nonstandard protein ligands

Area of Science:

• Biochemistry
• Materials Science
• Chemical Biology

Background:

• Congo red and related dyes self-associate in solution, forming liquid crystalline micelles.
• These dyes have been traditionally used for amyloid protein staining.
• Recent findings suggest these dyes can complex with native proteins in a unique manner.

Purpose of the Study:

• To investigate the non-standard complexation mechanism between self-assembling dyes and native proteins.
• To explore the role of protein structural dynamics in dye binding.
• To evaluate the functional consequences of dye binding on antibody-antigen interactions.

Main Methods:

• Utilized Immunoglobulin G (IgG) as a model protein to study dye binding.
• Investigated dye complexation with antibodies undergoing immune complexation.
• Assessed the impact of dye binding on antigen binding affinity and C1q complement attachment.
• Examined dye binding with other proteins like serpins.

Main Results:

• Confirmed that antibodies engaged in immune complexation bind liquid-crystalline dyes.
• Demonstrated that dye binding significantly enhances antigen binding to antibodies.
• Showed that dye binding inhibits the attachment of C1q to antibodies.
• Observed similar binding of supramolecular dyes to other proteins, including serpins.

Conclusions:

• Supramolecularity, arising from dye self-assembly, is key to forming non-standard protein ligands.
• The binding sites are likely protein structural gaps, potentially influenced by unfolding or ligand-induced fluctuations.
• These findings highlight potential therapeutic and experimental applications for supramolecular dyes in protein interactions.