The RanBP2/RanGAP1*SUMO1/Ubc9 complex: a multisubunit E3 ligase at the intersection of sumoylation and the RanGTPase cycle

Abstract

Posttranslational modification of proteins with SUMO and the RanGTP/GDP cycle are two essential cellular mechanisms contributing directly or indirectly to almost every cellular event. The SUMO E3 ligase RanBP2 (Nup358) and the Ran GTPase activating protein (RanGAP1) are known to form a stable complex throughout the cell cycle suggesting a link between sumoylation of proteins and RanGTP hydrolysis. In a recent study we demonstrated that the stable complex of RanBP2, sumoylated RanGAP1 and Ubc9 (and not RanBP2 by itself) represents the physiologically relevant form of the SUMO ligase. Characterization of the interactions reveals an intricate proximity of two catalytic activities, sumoylation and RanGTP hydrolysis. In this ExtraView we summarize our results and discuss some ideas about a potential coupling of both processes.

Figure 1. Cellular localization and schematic domain structure of RanBP2 with leucine-rich N-terminus (LR), four RanGTP binding domains (RB), an 8-fold zinc finger (ZF), a kinesin binding domain (KBD), a cyclophilin domain (CY), several FG repeats (dashes) and the SUMO E3 ligase region (E3) that is shown in more detail in the lower part. The complex with sumoylated RanGAP1 and Ubc9 is an active SUMO E3 ligase. Two internal repeats (IR) accommodate the binding site for stable interaction with sumoylated RanGAP1 and the structural Ubc9 (IR1) as well as the site for transient interaction with the catalytic Ubc9 (IR2). IR2 is only active in the context of the complex, in free RanBP2 its E3 ligase activity is negligible. The “core” region of the complex is flanked on both sides by RanGTP binding domains (RB) and FG repeats (dashes) that serve as interaction sites for RanGTP and transport receptors.