A naturally occurring 22-amino acid fragment of human hemoglobin A inhibits autophagy and HIV-1.
Autophagy
HIV
Hemoglobin
Innate immunity
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
17 Sep 2024
17 Sep 2024
Historique:
received:
03
07
2024
accepted:
10
09
2024
revised:
05
09
2024
medline:
18
9
2024
pubmed:
18
9
2024
entrez:
17
9
2024
Statut:
epublish
Résumé
Autophagy is an evolutionarily ancient catabolic pathway and has recently emerged as an integral part of the innate immune system. While the core machinery of autophagy is well defined, the physiological regulation of autophagy is less understood. Here, we identify a C-terminal fragment of human hemoglobin A (HBA1, amino acids 111-132) in human bone marrow as a fast-acting non-inflammatory inhibitor of autophagy initiation. It is proteolytically released from full-length HBA1 by cathepsin E, trypsin or pepsin. Biochemical characterization revealed that HBA1(111-132) has an in vitro stability of 52 min in human plasma and adopts a flexible monomeric conformation in solution. Structure-activity relationship studies revealed that the C-terminal 13 amino acids of HBA1(120-132) are sufficient to inhibit autophagy, two charged amino acids (D127, K128) mediate solubility, and two serines (S125, S132) are required for function. Successful viruses like human immunodeficiency virus 1 (HIV-1) evolved strategies to subvert autophagy for virion production. Our results show that HBA1(120-132) reduced virus yields of lab-adapted and primary HIV-1. Summarizing, our data identifies naturally occurring HBA1(111-132) as a physiological, non-inflammatory antagonist of autophagy. Optimized derivatives of HBA1(111-132) may offer perspectives to restrict autophagy-dependent viruses.
Identifiants
pubmed: 39289189
doi: 10.1007/s00018-024-05447-1
pii: 10.1007/s00018-024-05447-1
doi:
Substances chimiques
Peptide Fragments
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
409Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : CRC1279
Organisme : Deutsche Forschungsgemeinschaft
ID : SPP1923
Organisme : Deutsche Forschungsgemeinschaft
ID : SP 1600/7-1
Organisme : Deutsche Forschungsgemeinschaft
ID : SP 1600/9-1
Organisme : Deutsche Forschungsgemeinschaft
ID : CRC1279
Organisme : Deutsche Forschungsgemeinschaft
ID : CRC1279
Organisme : Deutsche Forschungsgemeinschaft
ID : CRC1279
Organisme : Deutsche Forschungsgemeinschaft
ID : CRC1279
Organisme : Deutsche Forschungsgemeinschaft
ID : INST 40/656-1
Organisme : Bundesministerium für Bildung und Forschung
ID : IMMUNOMOD
Informations de copyright
© 2024. The Author(s).
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