Structural highlights
Function
[TAXB1_HUMAN] Inhibits TNF-induced apoptosis by mediating the TNFAIP3 anti-apoptotic activity. Degraded by caspase-3-like family proteins upon TNF-induced apoptosis. May also play a role in the pro-inflammatory cytokine IL-1 signaling cascade.[1] [2]
Publication Abstract from PubMed
TAX1BP1 is a novel ubiquitin-binding adaptor protein involved in the negative regulation of the NF-kappaB transcription factor, which is a key player in inflammatory responses, immunity and tumorigenesis. TAX1BP1 recruits A20 to the ubiquitinated signaling proteins TRAF6 and RIP1, leading to their A20-mediated deubiquitination and the disruption of IL-1-induced and TNF-induced NF-kappaB signaling, respectively. The two zinc fingers localized at its C-terminus function as novel ubiquitin-binding domains (UBZ, ubiquitin-binding zinc finger). Here we present for the first time both the solution and crystal structures of two classical UBZ domains in tandem within the human TAX1BP1. The relative orientation of the two domains is slightly different in the X-ray structure with respect to the NMR structure, indicating some degree of conformational flexibility, which is rationalized by NMR relaxation data. The observed degree of flexibility and stability between the two UBZ domains might have consequences on the recognition mechanism of interacting partners.
The Structure of TAX1BP1 UBZ1+2 Provides Insight into Target Specificity and Adaptability.,Ceregido MA, Spinola Amilibia M, Buts L, Rivera-Torres J, Garcia-Pino A, Bravo J, van Nuland NA J Mol Biol. 2013 Nov 13. pii: S0022-2836(13)00717-1. doi:, 10.1016/j.jmb.2013.11.006. PMID:24239949[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ De Valck D, Jin DY, Heyninck K, Van de Craen M, Contreras R, Fiers W, Jeang KT, Beyaert R. The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases. Oncogene. 1999 Jul 22;18(29):4182-90. PMID:10435631 doi:http://dx.doi.org/10.1038/sj.onc.1202787
- ↑ Ling L, Goeddel DV. T6BP, a TRAF6-interacting protein involved in IL-1 signaling. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9567-72. PMID:10920205 doi:http://dx.doi.org/10.1073/pnas.170279097
- ↑ Ceregido MA, Spinola Amilibia M, Buts L, Rivera-Torres J, Garcia-Pino A, Bravo J, van Nuland NA. The Structure of TAX1BP1 UBZ1+2 Provides Insight into Target Specificity and Adaptability. J Mol Biol. 2013 Nov 13. pii: S0022-2836(13)00717-1. doi:, 10.1016/j.jmb.2013.11.006. PMID:24239949 doi:http://dx.doi.org/10.1016/j.jmb.2013.11.006
