A naturally occurring 22-amino acid fragment of human hemoglobin A inhibits autophagy and HIV-1

Abstract 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...
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Autor*in:	Freisem, Dennis [verfasserIn] Rodriguez-Alfonso, Armando A. [verfasserIn] Lawrenz, Jan [verfasserIn] Zhou, Zhixuan [verfasserIn] Monecke, Thomas [verfasserIn] Preising, Nico [verfasserIn] Endres, Sascha [verfasserIn] Wiese, Sebastian [verfasserIn] Ständker, Ludger [verfasserIn] Kuan, Seah-Ling [verfasserIn] Thal, Dietmar R. [verfasserIn] Weil, Tanja [verfasserIn] Niessing, Dierk [verfasserIn] Barth, Holger [verfasserIn] Kirchhoff, Frank [verfasserIn] Harms, Mirja [verfasserIn] Münch, Jan [verfasserIn] Sparrer, Konstantin M. J. [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Schlagwörter:	Hemoglobin Innate immunity HIV Autophagy

Anmerkung:	© The Author(s) 2024

Übergeordnetes Werk:	Enthalten in: Cellular and molecular life sciences - Springer International Publishing, 1997, 81(2024), 1 vom: 17. Sept.
Übergeordnetes Werk:	volume:81 ; year:2024 ; number:1 ; day:17 ; month:09

Links:	Volltext

DOI / URN:	10.1007/s00018-024-05447-1

Katalog-ID:	SPR057347425

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allfields	10.1007/s00018-024-05447-1 doi (DE-627)SPR057347425 (SPR)s00018-024-05447-1-e DE-627 ger DE-627 rakwb eng 570 610 VZ 42.15 bkl Freisem, Dennis verfasserin (orcid)0009-0008-9755-2261 aut A naturally occurring 22-amino acid fragment of human hemoglobin A inhibits autophagy and HIV-1 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract 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. Hemoglobin (dpeaa)DE-He213 Innate immunity (dpeaa)DE-He213 HIV (dpeaa)DE-He213 Autophagy (dpeaa)DE-He213 Rodriguez-Alfonso, Armando A. verfasserin aut Lawrenz, Jan verfasserin (orcid)0000-0003-3767-7130 aut Zhou, Zhixuan verfasserin aut Monecke, Thomas verfasserin aut Preising, Nico verfasserin aut Endres, Sascha verfasserin aut Wiese, Sebastian verfasserin aut Ständker, Ludger verfasserin aut Kuan, Seah-Ling verfasserin aut Thal, Dietmar R. verfasserin aut Weil, Tanja verfasserin aut Niessing, Dierk verfasserin aut Barth, Holger verfasserin aut Kirchhoff, Frank verfasserin (orcid)0000-0002-7052-2360 aut Harms, Mirja verfasserin (orcid)0000-0002-5460-5166 aut Münch, Jan verfasserin (orcid)0000-0001-7316-7141 aut Sparrer, Konstantin M. J. verfasserin (orcid)0000-0002-8682-1779 aut Enthalten in Cellular and molecular life sciences Springer International Publishing, 1997 81(2024), 1 vom: 17. Sept. (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:81 year:2024 number:1 day:17 month:09 https://dx.doi.org/10.1007/s00018-024-05447-1 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2050 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 42.15 VZ AR 81 2024 1 17 09
spelling	10.1007/s00018-024-05447-1 doi (DE-627)SPR057347425 (SPR)s00018-024-05447-1-e DE-627 ger DE-627 rakwb eng 570 610 VZ 42.15 bkl Freisem, Dennis verfasserin (orcid)0009-0008-9755-2261 aut A naturally occurring 22-amino acid fragment of human hemoglobin A inhibits autophagy and HIV-1 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract 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. Hemoglobin (dpeaa)DE-He213 Innate immunity (dpeaa)DE-He213 HIV (dpeaa)DE-He213 Autophagy (dpeaa)DE-He213 Rodriguez-Alfonso, Armando A. verfasserin aut Lawrenz, Jan verfasserin (orcid)0000-0003-3767-7130 aut Zhou, Zhixuan verfasserin aut Monecke, Thomas verfasserin aut Preising, Nico verfasserin aut Endres, Sascha verfasserin aut Wiese, Sebastian verfasserin aut Ständker, Ludger verfasserin aut Kuan, Seah-Ling verfasserin aut Thal, Dietmar R. verfasserin aut Weil, Tanja verfasserin aut Niessing, Dierk verfasserin aut Barth, Holger verfasserin aut Kirchhoff, Frank verfasserin (orcid)0000-0002-7052-2360 aut Harms, Mirja verfasserin (orcid)0000-0002-5460-5166 aut Münch, Jan verfasserin (orcid)0000-0001-7316-7141 aut Sparrer, Konstantin M. J. verfasserin (orcid)0000-0002-8682-1779 aut Enthalten in Cellular and molecular life sciences Springer International Publishing, 1997 81(2024), 1 vom: 17. Sept. (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:81 year:2024 number:1 day:17 month:09 https://dx.doi.org/10.1007/s00018-024-05447-1 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2050 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 42.15 VZ AR 81 2024 1 17 09
allfields_unstemmed	10.1007/s00018-024-05447-1 doi (DE-627)SPR057347425 (SPR)s00018-024-05447-1-e DE-627 ger DE-627 rakwb eng 570 610 VZ 42.15 bkl Freisem, Dennis verfasserin (orcid)0009-0008-9755-2261 aut A naturally occurring 22-amino acid fragment of human hemoglobin A inhibits autophagy and HIV-1 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract 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. Hemoglobin (dpeaa)DE-He213 Innate immunity (dpeaa)DE-He213 HIV (dpeaa)DE-He213 Autophagy (dpeaa)DE-He213 Rodriguez-Alfonso, Armando A. verfasserin aut Lawrenz, Jan verfasserin (orcid)0000-0003-3767-7130 aut Zhou, Zhixuan verfasserin aut Monecke, Thomas verfasserin aut Preising, Nico verfasserin aut Endres, Sascha verfasserin aut Wiese, Sebastian verfasserin aut Ständker, Ludger verfasserin aut Kuan, Seah-Ling verfasserin aut Thal, Dietmar R. verfasserin aut Weil, Tanja verfasserin aut Niessing, Dierk verfasserin aut Barth, Holger verfasserin aut Kirchhoff, Frank verfasserin (orcid)0000-0002-7052-2360 aut Harms, Mirja verfasserin (orcid)0000-0002-5460-5166 aut Münch, Jan verfasserin (orcid)0000-0001-7316-7141 aut Sparrer, Konstantin M. J. verfasserin (orcid)0000-0002-8682-1779 aut Enthalten in Cellular and molecular life sciences Springer International Publishing, 1997 81(2024), 1 vom: 17. Sept. (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:81 year:2024 number:1 day:17 month:09 https://dx.doi.org/10.1007/s00018-024-05447-1 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2050 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 42.15 VZ AR 81 2024 1 17 09
allfieldsGer	10.1007/s00018-024-05447-1 doi (DE-627)SPR057347425 (SPR)s00018-024-05447-1-e DE-627 ger DE-627 rakwb eng 570 610 VZ 42.15 bkl Freisem, Dennis verfasserin (orcid)0009-0008-9755-2261 aut A naturally occurring 22-amino acid fragment of human hemoglobin A inhibits autophagy and HIV-1 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract 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. Hemoglobin (dpeaa)DE-He213 Innate immunity (dpeaa)DE-He213 HIV (dpeaa)DE-He213 Autophagy (dpeaa)DE-He213 Rodriguez-Alfonso, Armando A. verfasserin aut Lawrenz, Jan verfasserin (orcid)0000-0003-3767-7130 aut Zhou, Zhixuan verfasserin aut Monecke, Thomas verfasserin aut Preising, Nico verfasserin aut Endres, Sascha verfasserin aut Wiese, Sebastian verfasserin aut Ständker, Ludger verfasserin aut Kuan, Seah-Ling verfasserin aut Thal, Dietmar R. verfasserin aut Weil, Tanja verfasserin aut Niessing, Dierk verfasserin aut Barth, Holger verfasserin aut Kirchhoff, Frank verfasserin (orcid)0000-0002-7052-2360 aut Harms, Mirja verfasserin (orcid)0000-0002-5460-5166 aut Münch, Jan verfasserin (orcid)0000-0001-7316-7141 aut Sparrer, Konstantin M. J. verfasserin (orcid)0000-0002-8682-1779 aut Enthalten in Cellular and molecular life sciences Springer International Publishing, 1997 81(2024), 1 vom: 17. Sept. (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:81 year:2024 number:1 day:17 month:09 https://dx.doi.org/10.1007/s00018-024-05447-1 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2050 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 42.15 VZ AR 81 2024 1 17 09
allfieldsSound	10.1007/s00018-024-05447-1 doi (DE-627)SPR057347425 (SPR)s00018-024-05447-1-e DE-627 ger DE-627 rakwb eng 570 610 VZ 42.15 bkl Freisem, Dennis verfasserin (orcid)0009-0008-9755-2261 aut A naturally occurring 22-amino acid fragment of human hemoglobin A inhibits autophagy and HIV-1 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract 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. Hemoglobin (dpeaa)DE-He213 Innate immunity (dpeaa)DE-He213 HIV (dpeaa)DE-He213 Autophagy (dpeaa)DE-He213 Rodriguez-Alfonso, Armando A. verfasserin aut Lawrenz, Jan verfasserin (orcid)0000-0003-3767-7130 aut Zhou, Zhixuan verfasserin aut Monecke, Thomas verfasserin aut Preising, Nico verfasserin aut Endres, Sascha verfasserin aut Wiese, Sebastian verfasserin aut Ständker, Ludger verfasserin aut Kuan, Seah-Ling verfasserin aut Thal, Dietmar R. verfasserin aut Weil, Tanja verfasserin aut Niessing, Dierk verfasserin aut Barth, Holger verfasserin aut Kirchhoff, Frank verfasserin (orcid)0000-0002-7052-2360 aut Harms, Mirja verfasserin (orcid)0000-0002-5460-5166 aut Münch, Jan verfasserin (orcid)0000-0001-7316-7141 aut Sparrer, Konstantin M. J. verfasserin (orcid)0000-0002-8682-1779 aut Enthalten in Cellular and molecular life sciences Springer International Publishing, 1997 81(2024), 1 vom: 17. Sept. (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:81 year:2024 number:1 day:17 month:09 https://dx.doi.org/10.1007/s00018-024-05447-1 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2050 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 42.15 VZ AR 81 2024 1 17 09
language	English
source	Enthalten in Cellular and molecular life sciences 81(2024), 1 vom: 17. Sept. volume:81 year:2024 number:1 day:17 month:09
sourceStr	Enthalten in Cellular and molecular life sciences 81(2024), 1 vom: 17. Sept. volume:81 year:2024 number:1 day:17 month:09
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Hemoglobin Innate immunity HIV Autophagy
dewey-raw	570
isfreeaccess_bool	true
container_title	Cellular and molecular life sciences
authorswithroles_txt_mv	Freisem, Dennis @@aut@@ Rodriguez-Alfonso, Armando A. @@aut@@ Lawrenz, Jan @@aut@@ Zhou, Zhixuan @@aut@@ Monecke, Thomas @@aut@@ Preising, Nico @@aut@@ Endres, Sascha @@aut@@ Wiese, Sebastian @@aut@@ Ständker, Ludger @@aut@@ Kuan, Seah-Ling @@aut@@ Thal, Dietmar R. @@aut@@ Weil, Tanja @@aut@@ Niessing, Dierk @@aut@@ Barth, Holger @@aut@@ Kirchhoff, Frank @@aut@@ Harms, Mirja @@aut@@ Münch, Jan @@aut@@ Sparrer, Konstantin M. J. @@aut@@
publishDateDaySort_date	2024-09-17T00:00:00Z
hierarchy_top_id	253390524
dewey-sort	3570
id	SPR057347425
language_de	englisch
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author	Freisem, Dennis
spellingShingle	Freisem, Dennis ddc 570 bkl 42.15 misc Hemoglobin misc Innate immunity misc HIV misc Autophagy A naturally occurring 22-amino acid fragment of human hemoglobin A inhibits autophagy and HIV-1
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topic_title	570 610 VZ 42.15 bkl A naturally occurring 22-amino acid fragment of human hemoglobin A inhibits autophagy and HIV-1 Hemoglobin (dpeaa)DE-He213 Innate immunity (dpeaa)DE-He213 HIV (dpeaa)DE-He213 Autophagy (dpeaa)DE-He213
topic	ddc 570 bkl 42.15 misc Hemoglobin misc Innate immunity misc HIV misc Autophagy
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title	A naturally occurring 22-amino acid fragment of human hemoglobin A inhibits autophagy and HIV-1
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title_full	A naturally occurring 22-amino acid fragment of human hemoglobin A inhibits autophagy and HIV-1
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author_browse	Freisem, Dennis Rodriguez-Alfonso, Armando A. Lawrenz, Jan Zhou, Zhixuan Monecke, Thomas Preising, Nico Endres, Sascha Wiese, Sebastian Ständker, Ludger Kuan, Seah-Ling Thal, Dietmar R. Weil, Tanja Niessing, Dierk Barth, Holger Kirchhoff, Frank Harms, Mirja Münch, Jan Sparrer, Konstantin M. J.
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title_sort	a naturally occurring 22-amino acid fragment of human hemoglobin a inhibits autophagy and hiv-1
title_auth	A naturally occurring 22-amino acid fragment of human hemoglobin A inhibits autophagy and HIV-1
abstract	Abstract 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. © The Author(s) 2024
abstractGer	Abstract 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. © The Author(s) 2024
abstract_unstemmed	Abstract 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. © The Author(s) 2024
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title_short	A naturally occurring 22-amino acid fragment of human hemoglobin A inhibits autophagy and HIV-1
url	https://dx.doi.org/10.1007/s00018-024-05447-1
remote_bool	true
author2	Rodriguez-Alfonso, Armando A. Lawrenz, Jan Zhou, Zhixuan Monecke, Thomas Preising, Nico Endres, Sascha Wiese, Sebastian Ständker, Ludger Kuan, Seah-Ling Thal, Dietmar R. Weil, Tanja Niessing, Dierk Barth, Holger Kirchhoff, Frank Harms, Mirja Münch, Jan Sparrer, Konstantin M. J.
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A naturally occurring 22-amino acid fragment of human hemoglobin A inhibits autophagy and HIV-1

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