Structural evaluation of SUMOlation activation in the human malaria parasite Plasmodium falciparum

Post-translational modifications of proteins by ubiquitin (Ub) and ubiquitin-like modifiers (Ubls) serves as an essential regulatory mechanism for fundamental cellular processes such as cell cycle progression, DNA damage repair, nucleus cytoplasmic transport, transcription and remodeling of chromatin. Modification of proteins by small ubiquitin-like modifiers (SUMOs) is mediated by the conjugation of the respective Ub/Ubls to target proteins, through the sequential interactions and activities of parallel cascades of enzymes that are structurally and mechanically related. E1 enzymes initiate SUMO conjugation cascades by catalyzing adenosine triphosphate (ATP)-dependent activation and transferring SUMO to the cognate conjugation site of the E2 enzyme, which then works with an array of E3 ligases to catalyze the formation of an isopeptide bond in which SUMO binds to target proteins. SUMO E1 is a ~110 kDa multidomain modular heterodimer composed of SUMO activating enzyme subunits 1 (Sae1) and 2 (Sae2) that harbor two catalytic activities required for SUMO activation.

Project details

Basic Science

Jun 2020 — Sep 2020

Brazil