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A review of Alpha-1 Antitrypsin binding partners for immune regulation and potential therapeutic application

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journal contribution
posted on 09.05.2022, 15:35 by Emmet O'BrienEmmet O'Brien, Grace Murray, Dedananda GogoiDedananda Gogoi, Azeez YusufAzeez Yusuf, Cormac McCarthy, Mark R. Wormald, Michelle CaseyMichelle Casey, Claudie Gabillard-Lefort, Noel G McElvaneyNoel G McElvaney, Emer ReevesEmer Reeves
Alpha-1 antitrypsin (AAT) is the canonical serine protease inhibitor of neutrophil-derived proteases and can modulate innate immune mechanisms through its anti-inflammatory activities mediated by a broad spectrum of protein, cytokine, and cell surface interactions. AAT contains a reactive methionine residue that is critical for its protease-specific binding capacity, whereby AAT entraps the protease on cleavage of its reactive centre loop, neutralises its activity by key changes in its tertiary structure, and permits removal of the AAT-protease complex from the circulation. Recently, however, the immunomodulatory role of AAT has come increasingly to the fore with several prominent studies focused on lipid or protein-protein interactions that are predominantly mediated through electrostatic, glycan, or hydrophobic potential binding sites. The aim of this review was to investigate the spectrum of AAT molecular interactions, with newer studies supporting a potential therapeutic paradigm for AAT augmentation therapy in disorders in which a chronic immune response is strongly linked.

Funding

US Alpha-1 Foundation (Grant # 615848)

Medical Research Charities Group/Health Research Board Joint Funding Scheme (Grant # MRCG-2018-04).

History

Comments

The original article is available at https://www.mdpi.com/

Published Citation

O'Brien ME, et al. A review of Alpha-1 Antitrypsin binding partners for immune regulation and potential therapeutic application. Int J Mol Sci. 2022;23(5):2441.

Publication Date

23 February 2022

PubMed ID

35269582

Department/Unit

  • Beaumont Hospital
  • Undergraduate Research
  • Medicine

Publisher

MDPI

Version

  • Published Version (Version of Record)