Martin, T.T.MartinLou, Y.-C.Y.-C.LouChou, C.-C.C.-C.ChouWei, S.-Y.S.-Y.WeiSadotra, S.S.SadotraCho, C.-C.C.-C.ChoLin, M.-H.M.-H.LinTai, J.-H.J.-H.TaiCHUN-HUA HSUChen, C.C.Chen2018-09-102018-09-102018http://www.scopus.com/inward/record.url?eid=2-s2.0-85044940577&partnerID=MN8TOARShttp://scholars.lib.ntu.edu.tw/handle/123456789/402828Cyclophilin 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. ? 2018 The Author(s).[SDGs]SDG3cyclophilin; 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 vaginalisjournal article10.1038/s41598-018-23821-52-s2.0-85044940577WOS:000428994100003