PMID- 30679605
OWN - NLM
STAT- MEDLINE
DCOM- 20200724
LR  - 20200724
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Jan 24
TI  - Interactions of HLA-DR and Topoisomerase I Epitope Modulated Genetic Risk for 
      Systemic Sclerosis.
PG  - 745
LID - 10.1038/s41598-018-37038-z [doi]
LID - 745
AB  - The association of systemic sclerosis with anti-Topoisomerase 1 antibody (ATASSc) 
      with specific alleles of human leukocyte antigen (HLA)-DR has been observed among 
      various ethnics. The anti-Topoisomerase 1 antibody is a common autoantibody in 
      SSc with diffuse cutaneous scleroderma, which is one of the clinical subtypes of 
      SSc. On the other hand, an immunodominant peptide of topoisomerase 1 (Top1) 
      self-protein (residues 349-368) was reported to have strong association with 
      ATASSc. In this study, molecular dynamics simulation was performed on the 
      complexes of Top1 peptide with various HLA-DR subtypes divided into 
      ATASSc-associated alleles (HLA-DRB1*08:02, HLA-DRB1*11:01 and HLA-DRB1*11:04), 
      suspected allele (HLA-DRB5*01:02), and non-associated allele (HLA-DRB1*01:01). 
      The unique interaction for each system was compared to the others in terms of 
      dynamical behaviors, binding free energies and solvation effects. Our results 
      showed that three HLA-DR/Top1 complexes of ATASSc association mostly exhibited 
      high protein stability and increased binding efficiency without solvent 
      interruption, in contrast to non-association. The suspected case (HLA-DRB5*01:02) 
      binds Top1 as strongly as the ATASSc association case, which implied a highly 
      possible risk for ATASSc development. This finding might support ATASSc 
      development mechanism leading to a guideline for the treatment and avoidance of 
      pathogens like Top1 self-peptide risk for ATASSc.
FAU - Kongkaew, Sirilak
AU  - Kongkaew S
AD  - Program in Biotechnology, Faculty of Science, Chulalongkorn University, Bangkok, 
      10330, Thailand.
AD  - The Center of Excellence in Computational Chemistry, Department of Chemistry, 
      Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
FAU - Rungrotmongkol, Thanyada
AU  - Rungrotmongkol T
AD  - Biocatalyst and Environmental Biotechnology Research unit, Department of 
      Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, 
      Thailand. t.rungrotmongkol@gmail.com.
AD  - Ph.D. Program in Bioinformatics and Computational Biology, Faculty of Science, 
      Chulalongkorn University, Bangkok, 10330, Thailand. t.rungrotmongkol@gmail.com.
FAU - Punwong, Chutintorn
AU  - Punwong C
AD  - Department of Physics, Faculty of Science, Prince of Songkla University, Hat Yai, 
      Songkhla, 90110, Thailand.
FAU - Noguchi, Hiroshi
AU  - Noguchi H
AD  - School of Pharmacy, Nihon Pharmaceutical University, Saitama, 361-0806, Japan.
AD  - School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, 
      Japan.
FAU - Takeuchi, Fujio
AU  - Takeuchi F
AD  - School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, 
      Japan.
AD  - Faculty of Health and Nutrition, Tokyo Seiei University, Tokyo, 124-8530, Japan.
FAU - Kungwan, Nawee
AU  - Kungwan N
AD  - Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai, 
      50200, Thailand.
AD  - Center of Excellence in Materials Science and Technology, Chiang Mai University, 
      Chiang Mai, 50200, Thailand.
FAU - Wolschann, Peter
AU  - Wolschann P
AD  - The Center of Excellence in Computational Chemistry, Department of Chemistry, 
      Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
AD  - Department of Pharmaceutical Chemistry, University of Vienna, Vienna, 1090, 
      Austria.
AD  - Institute of Theoretical Chemistry, University of Vienna, Vienna, 1090, Austria.
FAU - Hannongbua, Supot
AU  - Hannongbua S
AD  - The Center of Excellence in Computational Chemistry, Department of Chemistry, 
      Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand. 
      Supot.h@chula.ac.th.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190124
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antibodies, Anti-Idiotypic)
RN  - 0 (Epitopes)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB5 Chains)
RN  - 0 (Peptides)
RN  - EC 5.99.1.2 (DNA Topoisomerases, Type I)
SB  - IM
MH  - Alleles
MH  - Antibodies, Anti-Idiotypic/chemistry/genetics/immunology
MH  - DNA Topoisomerases, Type I/chemistry/*genetics/immunology
MH  - Epitopes/genetics/immunology
MH  - Genetic Predisposition to Disease
MH  - HLA-DRB1 Chains/*chemistry/genetics/immunology
MH  - HLA-DRB5 Chains/*chemistry/genetics/immunology
MH  - Humans
MH  - Molecular Dynamics Simulation
MH  - Peptides/chemistry/genetics/immunology
MH  - Protein Binding/genetics
MH  - Protein Stability
MH  - Risk Factors
MH  - Scleroderma, Systemic/*genetics/immunology/pathology
PMC - PMC6345791
COIS- The authors declare no competing interests.
EDAT- 2019/01/27 06:00
MHDA- 2020/07/25 06:00
PMCR- 2019/01/24
CRDT- 2019/01/26 06:00
PHST- 2018/01/26 00:00 [received]
PHST- 2018/11/29 00:00 [accepted]
PHST- 2019/01/26 06:00 [entrez]
PHST- 2019/01/27 06:00 [pubmed]
PHST- 2020/07/25 06:00 [medline]
PHST- 2019/01/24 00:00 [pmc-release]
AID - 10.1038/s41598-018-37038-z [pii]
AID - 37038 [pii]
AID - 10.1038/s41598-018-37038-z [doi]
PST - epublish
SO  - Sci Rep. 2019 Jan 24;9(1):745. doi: 10.1038/s41598-018-37038-z.