The C-terminal 32-mer fragment of hemoglobin alpha is an amyloidogenic peptide with antimicrobial properties

Cell Mol Life Sci. 2023 May 17;80(6):151. doi: 10.1007/s00018-023-04795-8.

Lia-Raluca Olari ¹, Richard Bauer ², Marta Gil Miró ¹, Verena Vogel ², Laura Cortez Rayas ³, Rüdiger Groß ¹, Andrea Gilg ¹, Raphael Klevesath ², Armando A Rodríguez Alfonso ⁴ ⁵, Kübra Kaygisiz ⁶, Ulrich Rupp ⁷, Pradeep Pant ⁸, Joel Mieres-Pérez ⁸, Lena Steppe ¹, Ramona Schäffer ¹, Lena Rauch-Wirth ¹, Carina Conzelmann ¹, Janis A Müller ⁹, Fabian Zech ¹, Fabian Gerbl ², Jana Bleher ¹⁰, Nico Preising ⁴, Ludger Ständker ⁴, Sebastian Wiese ⁵, Dietmar R Thal ¹¹ ¹², Christian Haupt ¹⁰, Hendrik R A Jonker ¹³, Manfred Wagner ⁶, Elsa Sanchez-Garcia ⁸, Tanja Weil ⁶, Steffen Stenger ², Marcus Fändrich ¹⁰, Jens von Einem ³, Clarissa Read ³ ⁷, Paul Walther ⁷, Frank Kirchhoff ¹, Barbara Spellerberg ², Jan Münch ¹⁴ ¹⁵

Affiliations

1 Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
2 Institute of Medical Microbiology and Hygiene, Ulm University Medical Center, 89081, Ulm, Germany.
3 Institute of Virology, Ulm University Medical Center, 89081, Ulm, Germany.
4 Core Facility for Functional Peptidomics, Ulm Peptide Pharmaceuticals (U-PEP), Ulm University Medical Center, 89081, Ulm, Germany.
5 Core Unit of Mass Spectrometry and Proteomics, Ulm University Medical Center, 89081, Ulm, Germany.
6 Max-Planck-Institute for Polymer Research Mainz, 55128, Mainz, Germany.
7 Central Facility for Electron Microscopy, Ulm University, 89081, Ulm, Germany.
8 Computational Biochemistry, Center of Medical Biotechnology, University of Duisburg-Essen, 45141, Essen, Germany.
9 Institute of Virology, Philipps University Marburg, 35043, Marburg, Germany.
10 Institute of Protein Biochemistry, Ulm University, 89081, Ulm, Germany.
11 Laboratory of Neuropathology, Department of Imaging and Pathology, Leuven Brain Institute, KU Leuven, Leuven, Belgium.
12 Department of Pathology, UZ-Leuven, 3000, Leuven, Belgium.
13 Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance, Goethe University, 60438, Frankfurt am Main, Germany.
14 Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany. [email protected].
15 Core Unit of Mass Spectrometry and Proteomics, Ulm University Medical Center, 89081, Ulm, Germany. [email protected].

PMID: 37198527 DOI: 10.1007/s00018-023-04795-8

Abstract

Antimicrobial Peptides (AMPs) are major components of the innate immune defense. Accumulating evidence suggests that the Antibacterial activity of many AMPs is dependent on the formation of amyloid-like fibrils. To identify novel fibril forming AMPs, we generated a spleen-derived peptide library and screened it for the presence of amyloidogenic Peptides. This approach led to the identification of a C-terminal 32-mer fragment of alpha-hemoglobin, termed HBA(111-142). The non-fibrillar peptide has membranolytic activity against various Bacterial species, while the HBA(111-142) fibrils aggregated bacteria to promote their phagocytotic clearance. Further, HBA(111-142) fibrils selectively inhibited measles and herpes viruses (HSV-1, HSV-2, HCMV), but not SARS-CoV-2, ZIKV and IAV. HBA(111-142) is released from its precursor by ubiquitous aspartic proteases under acidic conditions characteristic at sites of Infection and inflammation. Thus, HBA(111-142) is an amyloidogenic AMP that may specifically be generated from a highly abundant precursor during Bacterial or viral Infection and may play an important role in innate antimicrobial immune responses.

Keywords

AMP; Amyloid formation; Hemoglobin fragment; Membrane disruption; Proteolytic generation.

Products

Cat. No.

Product Name

Description

Target

Research Area
HY-P5693

HBA(111–142)

Antimicrobial Peptide

HSV; CMV; Bacterial

Infection

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