前骨髓性細胞白血病蛋白的結構和分子交互作用機制

Abstract

PML protein is mainly present inside the nucleus in the form of PML nuclear bodies (PML-NBs) and serves as a SUMO E3 ligase which facilitates SUMOylation on PML itself and proteins in PML-NBs. PML has a conserved N-terminal TRIM/RBCC region comprised of a RING finger domain, two B-boxes and a coiled-coil region. The purpose of this study is to investigate the structural basis of SUMOylation on PML TRIM domains which is essential in the formation of PML-NBs. However, not much of the structural information of PML is known today. In this work we solved the structures of RING finger and B-box 1 of dimer by advanced NMR techniques. We identified the residues involved in the binding of SUMO E2 enzyme Ubc9 and PML TRIM domains. The result of SPR indicated that dimeric domain RB1 showed much stronger interaction with Ubc9 (KD=16uM) than any single domain (KD=490uM for RING finger and KD=94uM for B-box 1), suggesting that RING finger and B-box 1 bound with Ubc9 in synergy. Here, we provide the structures of PML TRIM domains and the bindings with Ubc9 at molecular level in order to understand the SUMOylation mechanism on PML TRIM domains.