8I26

NMR structure of Toxoplasma gondii PDCD5 (cis form)

Summary for 8I26

• Entry DOI: 10.2210/pdb8i26/pdb
• Descriptor: Programmed cell death 5 protein (1 entity in total)
• Functional Keywords: molten globule, heparan sulfate/heparin binding protein, proline cis form, endocytosis
• Biological source: Toxoplasma gondii GT1
• Total number of polymer chains: 1
• Total formula weight: 13716.47

Authors

Lin, M.H.,Hsu, C.H. (deposition date: 2023-01-14, release date: 2024-01-17, Last modification date: 2024-06-12)

Primary citation

Lin, G.M.,Yu, T.A.,Chang, C.F.,Hsu, C.H.
Proline Isomerization and Molten Globular Property of TgPDCD5 Secreted from Toxoplasma gondii Confers Its Regulation of Heparin Sulfate Binding.
Jacs Au, 4:1763-1774, 2024

PubMed Abstract: Toxoplasmosis, caused by , poses risks to vulnerable populations. TgPDCD5, a secreted protein of , induces apoptosis through heparan sulfate-mediated endocytosis. The entry mechanism of TgPDCD5 has remained elusive. Here, we present the solution structure of TgPDCD5 as a helical bundle with an extended N-terminal helix, exhibiting molten globule characteristics. NMR perturbation studies reveal heparin/heparan sulfate binding involving the heparan sulfate/heparin proteoglycans-binding motif and the core region, influenced by proline isomerization of P107 residue. The heterogeneous proline recruits a cyclophilin TgCyp18, accelerating interconversion between conformers and regulating heparan/heparin binding. These atomic-level insights elucidate the binary switch's functionality, expose novel heparan sulfate-binding surfaces, and illuminate the unconventional cellular entry of pathogenic TgPDCD5.

PubMed: 38818051
DOI: 10.1021/jacsau.3c00577

Experimental method

SOLUTION NMR