Structural basis of interaction between dimeric cyclophilin 1 and Myb1 transcription factor in Trichomonas vaginalis
Journal
Scientific Reports
Journal Volume
8
Journal Volume
8
Journal Issue
1
Journal Issue
1
ISSN
20452322
Date Issued
2018-12-01
Author(s)
Martin, Tesmine
Lou, Yuan-Chao
Chou, Chun-Chi
Wei, Shu-Yi
Sadotra, Sushant
Cho, Chao-Cheng
Lin, Meng-Hsuan
Tai, Jung-Hsiang
Chen, Chinpan
Abstract
Cyclophilin 1 (TvCyP1), a cyclophilin type peptidyl-prolyl isomerase present in the human parasite Trichomonas vaginalis, interacts with Myb1 and assists in its nuclear translocation. Myb1 regulates the expression of ap65-1 gene that encodes for a disease causing cytoadherence enzyme. Here, we determined the crystal structures of TvCyP1 and its complex with the minimum TvCyP1-binding sequence of Myb1 (Myb1104-111), where TvCyP1 formed a homodimer, unlike other single domain cyclophilins. In the complex structure, one Myb1104-111 peptide was bound to each TvCyP1 protomer, with G106-P107 and Y105 fitting well into the active site and auxiliary S2 pocket, respectively. NMR data further showed that TvCyP1 can catalyze the cis/trans isomerization of P107 in Myb1104-111. Interestingly, in the well-folded Myb1 protein (Myb135-141), the minimum binding sequence adopted a different conformation from that of unstructured Myb1104-111 peptide, that could make P107 binding to the active site of TvCyP1 difficult. However, NMR studies showed that similar to Myb1104-111 peptide, Myb135-141 also interacted with the active site of TvCyP1 and the dynamics of the Myb135-141 residues near P107 was reduced upon interaction. Together, the structure of TvCyP1 and detailed structural insights on TvCyP1-Myb1 interaction provided here could pave the way for newer drugs to treat drug-resistant strains.
Other Subjects
cyclophilin; peptidylprolyl isomerase; protein binding; protozoal protein; transcription factor; binding site; chemistry; metabolism; molecular model; protein domain; protein multimerization; protein quaternary structure; protein stability; Trichomonas vaginalis; Binding Sites; Cyclophilins; Models, Molecular; Peptidylprolyl Isomerase; Protein Binding; Protein Domains; Protein Multimerization; Protein Stability; Protein Structure, Quaternary; Protozoan Proteins; Transcription Factors; Trichomonas vaginalis
Publisher
Nature Publishing Group
Description
Article number: 5410
Type
journal article