Structural Basis for the SUMO2 Isoform Specificity of SENP7

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• DeSUMOylases, also known as SUMO proteases, reverse SUMOylation by cleaving SUMO modifiers from protein targets.
• The SENP/ULP protease family, comprising six members, performs deSUMOylating activity in humans, all possessing a homologous catalytic domain.
• SENP6 and SENP7 are distinct members with a preference for SUMO2/3 isoforms and the ability to dismantle polySUMO2 chains.

Purpose of the Study:

• To elucidate the structural basis for the SUMO2 isoform specificity of the human SENP7 deSUMOylase.
• To reveal the key structural elements responsible for SENP7's selective interaction with SUMO2.

Main Methods:

• X-ray crystallography was employed to determine the structure of the catalytic domain of human SENP7 bound to SUMO2.
• Structural analysis focused on identifying specific interactions between SENP7 and SUMO2.

Main Results:

• The crystal structure of SENP7 bound to SUMO2 was determined, highlighting structural determinants of SUMO2 isoform specificity.
• A unique insertion in SENP7, termed Loop1, was identified as crucial for specific contacts with SUMO2, conferring isoform specificity.
• Other interaction interfaces, including the SUMO2 C-terminal tail interaction, were found to be conserved among SENP/ULP family members.

Conclusions:

• The study reveals the structural basis for SENP7's preference for SUMO2/3 isoforms through specific interactions mediated by Loop1.
• These findings provide insights into the evolutionary mechanisms that restrict the deSUMOylating activity of SENP6 and SENP7 to SUMO2/3 isoforms.