Omur Guven1, Halilibrahim Ciftci1, Hasan DeMirci1
1Koç University, 34450 Istanbul, Turkey
Tumor Necrosis Factor Receptor Associated Factors (TRAFs) are protein family with a wide variety of roles and binding partners. Among them, TRAF6, a ubiquitin ligase, possesses unique receptor binding specificity and shows diverse functions in immune system regulation, cellular signaling, central nervous system (CNS), and tumor formation. TRAF6 consists of an N-terminal RING domain, multiple zinc fingers, and a C-terminal TRAF domain. RING domain and zinc fingers mediate the activation of nuclear factor kappa B (NF-κB), which has essential roles in the regulation of inflammatory responses, proliferation, differentiation, migration, cell adhesion, and apoptosis. Therefore, it has been found that TRAF6 is overexpressed in various types of cancer, including pancreatic, along with inflammatory, autoimmune and neurodegenerative disorders. Furthermore, TRAF6 is an important therapeutic target for numerous disorders and structural studies of this protein are crucial for the development of next-generation therapeutics. Here, we present a TRAF6 N-terminal structure determined at the Turkish Light Source “Turkish DeLight” to 2.6 Å resolution at cryogenic temperature. This structure offers insight into the characteristics of the domain organization and zinc-binding, which are important for protein function and provide great insight for future therapeutics research.
Keywords: TRAF6; pancreatic cancer; zinc finger