The Double-Edged Sword of Beta2-Microglobulin in Antibacterial Properties and Amyloid Fibril-Mediated Cytotoxicity
Beta2-microglobulin (B2M) a key component of major histocompatibility complex class I molecules, which aid cytotoxic T-lymphocyte (CTL) immune response. However, the majority of studies of B2M have focused only on amyloid fibrils in pathogenesis to the neglect of its role of antimicrobial activity....
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doaj-11545c20a98549dca313ff7f24143f522021-07-01T00:05:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-01226330633010.3390/ijms22126330The Double-Edged Sword of Beta2-Microglobulin in Antibacterial Properties and Amyloid Fibril-Mediated CytotoxicityShean-Jaw Chiou0Huey-Jiun Ko1Chi-Ching Hwang2Yi-Ren Hong3Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanBeta2-microglobulin (B2M) a key component of major histocompatibility complex class I molecules, which aid cytotoxic T-lymphocyte (CTL) immune response. However, the majority of studies of B2M have focused only on amyloid fibrils in pathogenesis to the neglect of its role of antimicrobial activity. Indeed, B2M also plays an important role in innate defense and does not only function as an adjuvant for CTL response. A previous study discovered that human aggregated B2M binds the surface protein structure in <i>Streptococci</i>, and a similar study revealed that sB2M-9, derived from native B2M, functions as an antibacterial chemokine that binds <i>Staphylococcus aureus</i>. An investigation of sB2M-9 exhibiting an early lymphocyte recruitment in the human respiratory epithelium with bacterial challenge may uncover previously unrecognized aspects of B2M in the body’s innate defense against <i>Mycobactrium tuberculosis</i>. B2M possesses antimicrobial activity that operates primarily under pH-dependent acidic conditions at which B2M and fragmented B2M may become a nucleus seed that triggers self-aggregation into distinct states, such as oligomers and amyloid fibrils. Modified B2M can act as an antimicrobial peptide (AMP) against a wide range of microbes. Specifically, these AMPs disrupt microbe membranes, a feature similar to that of amyloid fibril mediated cytotoxicity toward eukaryotes. This study investigated two similar but nonidentical effects of B2M: the physiological role of B2M, in which it potentially acts against microbes in innate defense and the role of B2M in amyloid fibrils, in which it disrupts the membrane of pathological cells. Moreover, we explored the pH-governing antibacterial activity of B2M and acidic pH mediated B2M amyloid fibrils underlying such cytotoxicity.https://www.mdpi.com/1422-0067/22/12/6330beta2-microglobulinantimicrobial peptideamyloid fibrilscytotoxicity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shean-Jaw Chiou Huey-Jiun Ko Chi-Ching Hwang Yi-Ren Hong |
spellingShingle |
Shean-Jaw Chiou Huey-Jiun Ko Chi-Ching Hwang Yi-Ren Hong The Double-Edged Sword of Beta2-Microglobulin in Antibacterial Properties and Amyloid Fibril-Mediated Cytotoxicity International Journal of Molecular Sciences beta2-microglobulin antimicrobial peptide amyloid fibrils cytotoxicity |
author_facet |
Shean-Jaw Chiou Huey-Jiun Ko Chi-Ching Hwang Yi-Ren Hong |
author_sort |
Shean-Jaw Chiou |
title |
The Double-Edged Sword of Beta2-Microglobulin in Antibacterial Properties and Amyloid Fibril-Mediated Cytotoxicity |
title_short |
The Double-Edged Sword of Beta2-Microglobulin in Antibacterial Properties and Amyloid Fibril-Mediated Cytotoxicity |
title_full |
The Double-Edged Sword of Beta2-Microglobulin in Antibacterial Properties and Amyloid Fibril-Mediated Cytotoxicity |
title_fullStr |
The Double-Edged Sword of Beta2-Microglobulin in Antibacterial Properties and Amyloid Fibril-Mediated Cytotoxicity |
title_full_unstemmed |
The Double-Edged Sword of Beta2-Microglobulin in Antibacterial Properties and Amyloid Fibril-Mediated Cytotoxicity |
title_sort |
double-edged sword of beta2-microglobulin in antibacterial properties and amyloid fibril-mediated cytotoxicity |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-06-01 |
description |
Beta2-microglobulin (B2M) a key component of major histocompatibility complex class I molecules, which aid cytotoxic T-lymphocyte (CTL) immune response. However, the majority of studies of B2M have focused only on amyloid fibrils in pathogenesis to the neglect of its role of antimicrobial activity. Indeed, B2M also plays an important role in innate defense and does not only function as an adjuvant for CTL response. A previous study discovered that human aggregated B2M binds the surface protein structure in <i>Streptococci</i>, and a similar study revealed that sB2M-9, derived from native B2M, functions as an antibacterial chemokine that binds <i>Staphylococcus aureus</i>. An investigation of sB2M-9 exhibiting an early lymphocyte recruitment in the human respiratory epithelium with bacterial challenge may uncover previously unrecognized aspects of B2M in the body’s innate defense against <i>Mycobactrium tuberculosis</i>. B2M possesses antimicrobial activity that operates primarily under pH-dependent acidic conditions at which B2M and fragmented B2M may become a nucleus seed that triggers self-aggregation into distinct states, such as oligomers and amyloid fibrils. Modified B2M can act as an antimicrobial peptide (AMP) against a wide range of microbes. Specifically, these AMPs disrupt microbe membranes, a feature similar to that of amyloid fibril mediated cytotoxicity toward eukaryotes. This study investigated two similar but nonidentical effects of B2M: the physiological role of B2M, in which it potentially acts against microbes in innate defense and the role of B2M in amyloid fibrils, in which it disrupts the membrane of pathological cells. Moreover, we explored the pH-governing antibacterial activity of B2M and acidic pH mediated B2M amyloid fibrils underlying such cytotoxicity. |
topic |
beta2-microglobulin antimicrobial peptide amyloid fibrils cytotoxicity |
url |
https://www.mdpi.com/1422-0067/22/12/6330 |
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