Exploring Iron Withholding by the Innate Immune Protein Human Calprotectin.
Journal
Accounts of chemical research
ISSN: 1520-4898
Titre abrégé: Acc Chem Res
Pays: United States
ID NLM: 0157313
Informations de publication
Date de publication:
20 08 2019
20 08 2019
Historique:
pubmed:
6
8
2019
medline:
7
8
2020
entrez:
6
8
2019
Statut:
ppublish
Résumé
Calprotectin (CP) is a versatile player in the metal-withholding innate immune response, a process termed "nutritional immunity." CP is a heterooligomer of the polypeptides S100A8 and S100A9 and houses two transition-metal-binding sites at its S100A8/S100A9 heterodimer interface. During infection, CP is released from host cells and sequesters "bioavailable" transition metal ions in the extracellular space, thereby preventing microbial acquisition of these essential nutrients. For many years, the role of CP in nutritional immunity was interpreted in the contexts of Mn(II) and Zn(II) limitation, but recent work has broadened our understanding of its contributions to this process. We uncovered that CP provides a form of nutritional immunity that has previously received little attention: the battle between host and microbe for ferrous iron (Fe(II)). In this Account, we present our current understanding of Fe(II) coordination by CP and its role in Fe(II) withholding as well as considerations for future discovery. Nutritional immunity was first described in the context of host-microbe competition for ferric iron (Fe(III)). The battle for Fe(II) has received comparably little attention because the abundance of Fe(II) at infection sites and the importance of Fe(II) acquisition for microbial pathogenesis were recognized only recently. Several years ago, we discovered that human CP sequesters Fe(II) at its His
Identifiants
pubmed: 31381301
doi: 10.1021/acs.accounts.9b00250
pmc: PMC6702060
mid: NIHMS1040833
doi:
Substances chimiques
Leukocyte L1 Antigen Complex
0
Histidine
4QD397987E
Iron
E1UOL152H7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2301-2308Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM118695
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM126376
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI095190
Pays : United States
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