Backbone and nearly complete side-chain chemical shift assignments of the human death-associated protein 1 (DAP1)
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ARTICLE
Backbone and nearly complete side‑chain chemical shift assignments of the human death‑associated protein 1 (DAP1) Christoph Wiedemann1 · Johanna Voigt1 · Jan Jirschitzka2 · Sabine Häfner3 · Oliver Ohlenschläger3 · Frank Bordusa1 Received: 2 October 2020 / Accepted: 16 November 2020 © The Author(s) 2020
Abstract Death-associated protein 1 (DAP1) is a proline-rich cytoplasmatic protein highly conserved in most eukaryotes. It has been reported to be involved in controlling cell growth and migration, autophagy and apoptosis. The presence of human DAP1 is associated to a favourable prognosis in different types of cancer. Here we describe the almost complete 1 H , 13 C , and 15 N chemical shift assignments of the human DAP1. The limited spectral dispersion, mainly in the 1 HN region, and the lack of defined secondary structure elements, predicted based on chemical shifts, identifies human DAP1 as an intrinsically disordered protein (IDP). This work lays the foundation for further structural investigations, dynamic studies, mapping of potential interaction partners or drug screening and development. Keywords Death-associated protein 1 · Human · Intrinsically disordered protein · IDP · Cell growth · Cell migration · Autophagy · Apoptosis · resonance assignment · Chemical shifts
Biological context The human Death-associated protein 1 (DAP1) is a member of the DAP family (DAP1-5)—originally identified as a diverse group of proteins that constitute biochemical pathways leading to apoptosis (Levy-Strumpf and Kimchi 1998). DAP1 is highly conserved in most eukaryotes and ubiquitously expressed in many cells and tissues. It was originally discovered in HeLa-cells, which were under the constant influence of apoptosis-inducing IFN-γ (Deiss et al. 1995). The high sequence homology especially within higher eukaryotes (Fig. 1) raises the question whether DAP1 is a young protein in evolutionary terms or whether the strong
* Christoph Wiedemann [email protected]‑halle.de 1
Institute of Biochemistry and Biotechnology, Charles Tanford Protein Centre, Martin Luther University HalleWittenberg, Kurt‑Mothes‑Str. 3a, 06120 Halle, Germany
2
Department of Chemistry, Institute of Biochemistry, University of Cologne, Zülpicher Str. 47, 50674 Cologne, Germany
3
Leibniz Institute on Aging - Fritz Lipmann Institute, Beutenbergstr. 11, 07745 Jena, Germany
sequence conservation is a prerequisite for a fundamental function of DAP1 identical in all higher organisms. The human DAP1 gene encodes for a cytoplasmatic protein (UniProtKB - P51397) of 102 amino acid with a proline content of nearly 15%. Human cell line experiments identified DAP1 as a phosphoprotein (S3 and S51 are phosphorylated) under nutrient-rich conditions. However, stress conditions trigger rapid dephosphorylation of DAP1 (Koren et al. 2010b). The downstream effectors of DAP1 are still subject of intensive research (Yahiro et al. 2014; Nie et al. 2020), but a proposed candidate for upstream regulation is mTOR (Koren et al. 2010a, b). The
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