Design of a specific peptide against phenolic glycolipid-1 from Mycobacterium leprae and its implications in leprosy bacilli entry.
Journal
Memorias do Instituto Oswaldo Cruz
ISSN: 1678-8060
Titre abrégé: Mem Inst Oswaldo Cruz
Pays: Brazil
ID NLM: 7502619
Informations de publication
Date de publication:
2022
2022
Historique:
received:
26
01
2022
accepted:
14
06
2022
entrez:
20
7
2022
pubmed:
21
7
2022
medline:
23
7
2022
Statut:
epublish
Résumé
Mycobacterium leprae, the causative agent of Hansen's disease, causes neural damage through the specific interaction between the external phenolic glycolipid-1 (PGL-1) and laminin subunit alpha-2 (LAMA2) from Schwann cells. To design a LAMA2-based peptide that targets PGL-1 from M. leprae. We retrieved the protein sequence of human LAMA2 and designed a specific peptide using the Antimicrobial Peptide Database and physicochemical parameters for antimycobacterial peptide-lipid interactions. We used the AlphaFold2 server to predict its three-dimensional structure, AUTODOCK-VINA for docking, and GROMACS programs for molecular dynamics simulations. We analysed 52 candidate peptides from LAMA2, and subsequent screening resulted in a single 60-mer peptide. The mapped peptide comprises four β-sheets and a random coiled region. This peptide exhibits a 45% hydrophobic ratio, in which one-third covers the same surface. Molecular dynamics simulations show that our predicted peptide is stable in aqueous solution and remains stable upon interaction with PGL-1 binding. In addition, we found that PGL-1 has a preference for one of the two faces of the predicted peptide, which could act as the preferential binding site of PGL-1. Our LAMA2-based peptide targeting PGL-1 might have the potential to specifically block this key molecule, suggesting that the preferential region of the peptide is involved in the initial contact during the attachment of leprosy bacilli to Schwann cells.
Sections du résumé
BACKGROUND
BACKGROUND
Mycobacterium leprae, the causative agent of Hansen's disease, causes neural damage through the specific interaction between the external phenolic glycolipid-1 (PGL-1) and laminin subunit alpha-2 (LAMA2) from Schwann cells.
OBJECTIVE
OBJECTIVE
To design a LAMA2-based peptide that targets PGL-1 from M. leprae.
METHODS
METHODS
We retrieved the protein sequence of human LAMA2 and designed a specific peptide using the Antimicrobial Peptide Database and physicochemical parameters for antimycobacterial peptide-lipid interactions. We used the AlphaFold2 server to predict its three-dimensional structure, AUTODOCK-VINA for docking, and GROMACS programs for molecular dynamics simulations.
FINDINGS
RESULTS
We analysed 52 candidate peptides from LAMA2, and subsequent screening resulted in a single 60-mer peptide. The mapped peptide comprises four β-sheets and a random coiled region. This peptide exhibits a 45% hydrophobic ratio, in which one-third covers the same surface. Molecular dynamics simulations show that our predicted peptide is stable in aqueous solution and remains stable upon interaction with PGL-1 binding. In addition, we found that PGL-1 has a preference for one of the two faces of the predicted peptide, which could act as the preferential binding site of PGL-1.
MAIN CONCLUSIONS
CONCLUSIONS
Our LAMA2-based peptide targeting PGL-1 might have the potential to specifically block this key molecule, suggesting that the preferential region of the peptide is involved in the initial contact during the attachment of leprosy bacilli to Schwann cells.
Identifiants
pubmed: 35857971
pii: S0074-02762022000101115
doi: 10.1590/0074-02760220025
pmc: PMC9296141
pii:
doi:
Substances chimiques
Antibodies, Bacterial
0
Antigens, Bacterial
0
Glycolipids
0
Peptides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e220025Références
Bioinformatics. 2019 Aug 15;35(16):2856-2858
pubmed: 30615063
Cell. 1997 Mar 21;88(6):811-21
pubmed: 9118224
J Mol Biol. 1998 Feb 6;275(5):725-30
pubmed: 9480764
Nat Methods. 2022 Jun;19(6):679-682
pubmed: 35637307
Nature. 2021 Aug;596(7873):583-589
pubmed: 34265844
Future Med Chem. 2017 Mar;9(3):275-291
pubmed: 28211294
Arch Microbiol. 2021 Oct;203(8):4891-4899
pubmed: 34244831
J Chem Inf Model. 2011 Oct 24;51(10):2778-86
pubmed: 21919503
Cell Res. 2009 Feb;19(2):271-3
pubmed: 19153597
Protein Sci. 2018 Jan;27(1):293-315
pubmed: 29067766
J Bacteriol. 1981 Sep;147(3):728-35
pubmed: 7024248
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
J Chem Inf Model. 2021 Oct 25;61(10):4827-4831
pubmed: 34586808
Curr Opin Microbiol. 2001 Feb;4(1):21-7
pubmed: 11173029
Chembiochem. 2021 Apr 16;22(8):1487-1493
pubmed: 33332701
Microbes Infect. 2005 Jul;7(9-10):1097-109
pubmed: 15919224
Lancet Infect Dis. 2017 Sep;17(9):e293-e297
pubmed: 28693853
Biochimie. 2017 Oct;141:3-8
pubmed: 28322927
Biotechnol Adv. 2021 Dec;53:107834
pubmed: 34509601
Brief Bioinform. 2021 Jul 20;22(4):
pubmed: 33201237
BMC Bioinformatics. 2008 Jan 23;9:40
pubmed: 18215316
J Mol Biol. 1982 May 5;157(1):105-32
pubmed: 7108955
Front Mol Biosci. 2021 May 07;8:663301
pubmed: 34026836
J Biol Chem. 2009 Aug 21;284(34):22786-92
pubmed: 19553699
Nucleic Acids Res. 2016 Jan 4;44(D1):D1087-93
pubmed: 26602694
J Mol Model. 2019 Nov 25;25(12):355
pubmed: 31768713
Pac Symp Biocomput. 2002;:310-22
pubmed: 11928486
Nucleic Acids Res. 2018 Jan 4;46(D1):D493-D496
pubmed: 29040681
PLoS Comput Biol. 2013;9(10):e1003249
pubmed: 24098099
BMC Res Notes. 2012 Jul 23;5:367
pubmed: 22824207
Cell Microbiol. 2020 Jan;22(1):e13128
pubmed: 31652371
Sci Rep. 2016 Aug 18;6:32153
pubmed: 27535582
Mol Cell. 1999 Nov;4(5):783-92
pubmed: 10619025
J Comput Chem. 2010 Jan 30;31(2):455-61
pubmed: 19499576
Clin Dermatol. 2015 Jan-Feb;33(1):90-8
pubmed: 25432814
J Cell Biol. 2004 Mar 29;164(7):959-63
pubmed: 15037599
Antimicrob Agents Chemother. 2016 Apr 22;60(5):2757-64
pubmed: 26902758
Science. 2013 Apr 26;340(6131):479-83
pubmed: 23519211
J Biol Chem. 2020 Jan 31;295(5):1202-1211
pubmed: 31852737
Pharmaceutics. 2020 Dec 11;12(12):
pubmed: 33322356
PLoS One. 2013 Sep 13;8(9):e73957
pubmed: 24058508
Nat Rev Drug Discov. 2017 Jul;16(7):457-471
pubmed: 28337021
Curr Top Microbiol Immunol. 2002;262:111-37
pubmed: 11987803
J Membr Biol. 2021 Feb;254(1):17-28
pubmed: 33196888
Nat Struct Biol. 1996 Oct;3(10):842-8
pubmed: 8836100
Biomedica. 2014 Apr;34 Suppl 1:137-47
pubmed: 24968045
Acta Trop. 2019 Sep;197:105041
pubmed: 31152726
Proteomes. 2021 Jan 29;9(1):
pubmed: 33573064
Curr Opin Struct Biol. 2020 Apr;61:160-166
pubmed: 32006812
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):16071-6
pubmed: 14657400
Acta Biomater. 2015 Dec;28:99-108
pubmed: 26380930
Cell. 2000 Oct 27;103(3):511-24
pubmed: 11081637
J Am Acad Dermatol. 2020 Jul;83(1):17-30
pubmed: 32244016
Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W177-81
pubmed: 16844986
J Biol Chem. 2002 Aug 30;277(35):32086-93
pubmed: 12065592
Int J Mol Sci. 2021 Aug 04;22(16):
pubmed: 34445098
Rev Soc Bras Med Trop. 2015 Nov-Dec;48(6):739-45
pubmed: 26676499
Proteins. 2010 Jun;78(8):1950-8
pubmed: 20408171
Infect Immun. 2021 Mar 17;89(4):
pubmed: 33558318