A review of Alpha-1 Antitrypsin binding partners for immune regulation and potential therapeutic application
journal contributionposted on 09.05.2022, 15:35 authored 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.
US Alpha-1 Foundation (Grant # 615848)
Medical Research Charities Group/Health Research Board Joint Funding Scheme (Grant # MRCG-2018-04).
CommentsThe original article is available at https://www.mdpi.com/
Published CitationO'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 Date23 February 2022
- Beaumont Hospital
- Undergraduate Research
- Published Version (Version of Record)