| Autor: |
Singh, Jai Shankar, Sajeev, T.K., Panigrahi, Rajlaxmi, Cherry, Pearl, Panchakshari, Nimisha Abhay, Shukla, Vaibhav Kumar, Kumar, Ashutosh, Mishra, Ram Kumar |
| Zdroj: |
Biophysical Journal; 20220101, Issue: Preprints |
| Abstrakt: |
The endoparasitic pathogen, Plasmodium falciparum(Pf), modulates protein-protein interactions to employ post-translational modifications like SUMOylation to establish successful infections. The interaction between E1 and E2 (Ubc9) enzymes governs species specificity in the PlasmodiumSUMOylation pathway. Here, we demonstrate that a unidirectional cross-species interaction exists between Pf-SUMO and human E2, whereas Hs-SUMO1 failed to interact with Pf-E2. Biochemical and biophysical analyses revealed that surface-accessible aspartates of Pf-SUMO determine the efficacy and specificity of SUMO-Ubc9 interactions. Furthermore, we demonstrate that critical residues of the Pf-Ubc9 N terminus are responsible for diminished Hs-SUMO1 and Pf-Ubc9 interaction. Mutating these residues to corresponding Hs-Ubc9 residues restores electrostatic, π−π, and hydrophobic interactions and allows efficient cross-species interactions. We suggest that, in comparison with human counterparts, PlasmodiumSUMO and Ubc9 proteins have acquired critical changes on their surfaces as nodes, which Plasmodiumcan use to exploit the host SUMOylation machinery. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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