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
NDP52 and TAX1BP1, two SKIP carboxyl homology (SKICH) domain-containing autophagy receptors, play crucial roles in selective autophagy. The autophagic functions of NDP52 and TAX1BP1 are regulated by TANK-binding kinase 1 (TBK1), which may associate with them through the adaptor NAP1. However, the molecular mechanism governing the interactions of NAP1 with NDP52 and TAX1BP1, as well as the effects induced by TBK1-mediated phosphorylation of NDP52 and TAX1BP1, remains elusive. Here, we report the atomic structures of the SKICH regions of NDP52 and TAX1BP1 in complex with NAP1, which not only uncover the mechanistic bases underpinning the specific interactions of NAP1 with the SKICH domains of NDP52 and TAX1BP1 but also reveal the binding mode of a SKICH domain. Moreover, we uncovered that the SKICH domains of NDP52 and TAX1BP1 share a general binding mode to interact with NAP1. Finally, we also evaluated the currently known TBK1-mediated phosphorylation sites in the SKICH domains of NDP52 and TAX1BP1 on the basis of their interactions with NAP1. In all, our findings provide mechanistic insights into the interactions of NAP1 with NDP52 and TAX1BP1, and are valuable for further understanding the functions of these proteins in selective autophagy.
Mechanistic insights into the interactions of NAP1 with the SKICH domains of NDP52 and TAX1BP1.,Fu T, Liu J, Wang Y, Xie X, Hu S, Pan L Proc Natl Acad Sci U S A. 2018 Dec 11;115(50):E11651-E11660. doi:, 10.1073/pnas.1811421115. Epub 2018 Nov 20. PMID:30459273[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
- ↑ Fu T, Liu J, Wang Y, Xie X, Hu S, Pan L. Mechanistic insights into the interactions of NAP1 with the SKICH domains of NDP52 and TAX1BP1. Proc Natl Acad Sci U S A. 2018 Dec 11;115(50):E11651-E11660. doi:, 10.1073/pnas.1811421115. Epub 2018 Nov 20. PMID:30459273 doi:http://dx.doi.org/10.1073/pnas.1811421115
