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Publication Abstract from PubMed

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 (Myb1(104-111)), where TvCyP1 formed a homodimer, unlike other single domain cyclophilins. In the complex structure, one Myb1(104-111) 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 Myb1(104-111). Interestingly, in the well-folded Myb1 protein (Myb1(35-141)), the minimum binding sequence adopted a different conformation from that of unstructured Myb1(104-111) peptide, that could make P107 binding to the active site of TvCyP1 difficult. However, NMR studies showed that similar to Myb1(104-111) peptide, Myb1(35-141) also interacted with the active site of TvCyP1 and the dynamics of the Myb1(35-141) 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.

Structural basis of interaction between dimeric cyclophilin 1 and Myb1 transcription factor in Trichomonas vaginalis.,Martin T, Lou YC, Chou CC, Wei SY, Sadotra S, Cho CC, Lin MH, Tai JH, Hsu CH, Chen C Sci Rep. 2018 Apr 3;8(1):5410. doi: 10.1038/s41598-018-23821-5. PMID:29615721^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.