LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases
Antimicrobial peptides (AMPs), as well as host defense peptides (HDPs), constitute the first line of defense as part of the innate immune system. Humans are known to express antimicrobial precursor proteins, which are further processed to generate AMPs, including several types of α/β defensins, hist...
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MDPI AG
2024-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/14/3/320 |
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| author | Surajit Bhattacharjya Zhizhuo Zhang Ayyalusamy Ramamoorthy |
| author_facet | Surajit Bhattacharjya Zhizhuo Zhang Ayyalusamy Ramamoorthy |
| author_sort | Surajit Bhattacharjya |
| collection | DOAJ |
| description | Antimicrobial peptides (AMPs), as well as host defense peptides (HDPs), constitute the first line of defense as part of the innate immune system. Humans are known to express antimicrobial precursor proteins, which are further processed to generate AMPs, including several types of α/β defensins, histatins, and cathelicidin-derived AMPs like LL37. The broad-spectrum activity of AMPs is crucial to defend against infections caused by pathogenic bacteria, viruses, fungi, and parasites. The emergence of multi-drug resistant pathogenic bacteria is of global concern for public health. The prospects of targeting antibiotic-resistant strains of bacteria with AMPs are of high significance for developing new generations of antimicrobial agents. The 37-residue long LL37, the only cathelicidin family of AMP in humans, has been the major focus for the past few decades of research. The host defense activity of LL37 is likely underscored by its expression throughout the body, spanning from the epithelial cells of various organs—testis, skin, respiratory tract, and gastrointestinal tract—to immune cells. Remarkably, apart from canonical direct killing of pathogenic organisms, LL37 exerts several other host defense activities, including inflammatory response modulation, chemo-attraction, and wound healing and closure at the infected sites. In addition, LL37 and its derived peptides are bestowed with anti-cancer and anti-amyloidogenic properties. In this review article, we aim to develop integrative, mechanistic insight into LL37 and its derived peptides, based on the known biophysical, structural, and functional studies in recent years. We believe that this review will pave the way for future research on the structures, biochemical and biophysical properties, and design of novel LL37-based molecules. |
| first_indexed | 2024-04-24T18:29:58Z |
| format | Article |
| id | doaj.art-461004323080430daa86aada4d2726b9 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-04-24T18:29:58Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-461004323080430daa86aada4d2726b92024-03-27T13:27:57ZengMDPI AGBiomolecules2218-273X2024-03-0114332010.3390/biom14030320LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related DiseasesSurajit Bhattacharjya0Zhizhuo Zhang1Ayyalusamy Ramamoorthy2School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, SingaporeDepartment of Chemistry, Biomedical Engineering, Macromolecular Science and Engineering, Michigan Neuroscience Institute, The University of Michigan, Ann Arbor, MI 48109, USADepartment of Chemistry, Biomedical Engineering, Macromolecular Science and Engineering, Michigan Neuroscience Institute, The University of Michigan, Ann Arbor, MI 48109, USAAntimicrobial peptides (AMPs), as well as host defense peptides (HDPs), constitute the first line of defense as part of the innate immune system. Humans are known to express antimicrobial precursor proteins, which are further processed to generate AMPs, including several types of α/β defensins, histatins, and cathelicidin-derived AMPs like LL37. The broad-spectrum activity of AMPs is crucial to defend against infections caused by pathogenic bacteria, viruses, fungi, and parasites. The emergence of multi-drug resistant pathogenic bacteria is of global concern for public health. The prospects of targeting antibiotic-resistant strains of bacteria with AMPs are of high significance for developing new generations of antimicrobial agents. The 37-residue long LL37, the only cathelicidin family of AMP in humans, has been the major focus for the past few decades of research. The host defense activity of LL37 is likely underscored by its expression throughout the body, spanning from the epithelial cells of various organs—testis, skin, respiratory tract, and gastrointestinal tract—to immune cells. Remarkably, apart from canonical direct killing of pathogenic organisms, LL37 exerts several other host defense activities, including inflammatory response modulation, chemo-attraction, and wound healing and closure at the infected sites. In addition, LL37 and its derived peptides are bestowed with anti-cancer and anti-amyloidogenic properties. In this review article, we aim to develop integrative, mechanistic insight into LL37 and its derived peptides, based on the known biophysical, structural, and functional studies in recent years. We believe that this review will pave the way for future research on the structures, biochemical and biophysical properties, and design of novel LL37-based molecules.https://www.mdpi.com/2218-273X/14/3/320antimicrobial peptideshost defense peptidesLL37structurebiophysicalhuman antimicrobial peptides |
| spellingShingle | Surajit Bhattacharjya Zhizhuo Zhang Ayyalusamy Ramamoorthy LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases Biomolecules antimicrobial peptides host defense peptides LL37 structure biophysical human antimicrobial peptides |
| title | LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases |
| title_full | LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases |
| title_fullStr | LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases |
| title_full_unstemmed | LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases |
| title_short | LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases |
| title_sort | ll 37 structures antimicrobial activity and influence on amyloid related diseases |
| topic | antimicrobial peptides host defense peptides LL37 structure biophysical human antimicrobial peptides |
| url | https://www.mdpi.com/2218-273X/14/3/320 |
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