UBC13 MMS2

From Proteopedia

Revision as of 18:03, 21 February 2015

Summary

Ubc13 is an E2 ubiquitin conjugating enzyme that lacks function without forming a heterodimer with Mms2. Ubc13 is involved in pathways that repair double stranded damage in DNA molecules. When bound to Mms2, Ubc13 will polyubiquinate PCNA, proliferating cell nuclear antigen. Many proteins that Ubc13 interacts with are RING finger proteins such as Traf6.

Function

UBC13 functions as a heterodimer with MMS2, a structurally similar protein to UBC13, but lacking the catalytic Cysteine residue in the active site. The UBC13 E2 complex with MMS2 functions primarily to enhance DNA repair from double stranded breaks.

Inhibitors

Coordinating Enzymes

• Another E2 complex, Rad6-Rad18, starts the process of DNA repair by monoubiquinating PCNA near the replication fork of DNA. This DNA repair will arrest cell cycle progression until DNA repair is complete.
• UEV1A, another cofactor enzyme that binds to UBC13, is thought to compete with MMS2 for binding to UBC13. This is thought to be a regulatory mechanism for UBC13 activity in the nucleus of cells.

Pathway for DNA Repair

Structural Highlights/Important Residues

Ubc13 weights 17.6 kDA, and Mms2 is 16.8 kDA. The heterodimer is stable at high stalt concentrations (1 M), suggesting strong interactions between the two. Kd between the Ubc13 and Mms2 is 2 uM. Phe57 and Glu55 of Ubc13 interact with the N-terminal domain of Mms2 to ensure stable docking. Additionally, Arg70 hydrophobically interacts with an alpha helix of Mms2 in two places. Mms2’s Phe13 is inserted between Glu55, Phe57, and Arg70 of Ubc13 to create a hydrophobic pocket. It is therorized that Glu55 and Arg70 of Ubc13 are more important for recognition instead of stability.

Mechanism

The exact mechanism for how Ubc13 transfers ubiquitin is not known, however the mechanism is either occurs in a step-wise or concerted reaction.

References

PAGE NOT YET COMPLETE, REFERENCES TO COME WITHIN A WEEK (3/1/15)