The innate immune system protects against foreign microorganisms by triggering inflammatory response. There are a couple of pathways that involve dozens of proteins including nuclear factor-?� (NF-?�) and interferon regulatory factor 3 (IRF3). These pathways lead to inflammation to fight disease. However, excessive inflammation leads to pathogenicity of certain diseases, such as inflammatory diseases. TAX-1 (T-lymphotropic virus type 1) binding protein 1 (TAX1BP1) plays an essential role in negatively regulating the NF-?� and IRF3 mediated proinflammatory pathways. TAX1BP1 was originally identified as the binding protein of TAX1. It was shown later that TAX1BP1 also interacted with other proteins such as the A20 enzyme, a ubiquitin editing enzyme. In the anti-inflammatory pathway, TAX1BP1 can coordinate with A20 to inhibit the release of IRF3 and NF-?�. Furthermore, TAX1BP1 can negatively regulate tumor necrosis factor (TNF)-induced cell death. There is also evidence that TAX1BP1 can regulate cell growth. However, the mechanisms of these functions of TAX1BP1 are largely unknown. It is beneficial to study the structure of TAX1BP1 to understand these mechanisms. TAX1BP1 is a highly conserved protein across species. Human TAX1BP1 contains 747 amino acids with three speculated domains: an N-terminal skich domain, a coiled-coil domain in the middle, and two zinc finger domains at the C-terminus. The zinc finger domains contains PPXY motif which is responsible for binding of WW domain containing proteins. The function of the skich domain remains unknown. Although skich domains have been described as membrane targeting domains, this function has not been described for TAX1BP1. In our study, we crystallized the TAX1BP1 skich domain and solved the structure of this domain at a resolution of 1.9 �. We are currently working on the structure analysis and crystallization trials of other bigger protein constructs of TAX1BP1.

Crystal structure of TAX-1 (T-lymphotropic virus type 1) binding protein 1 (TAX1BP1) skich domain

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.