2. Academic Validation
  3. The C-terminal 32-mer fragment of hemoglobin alpha is an amyloidogenic peptide with antimicrobial properties

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

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. jan.muench@uni-ulm.de.
  • 15 Core Unit of Mass Spectrometry and Proteomics, Ulm University Medical Center, 89081, Ulm, Germany. jan.muench@uni-ulm.de.
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.

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