Identification of topological determinants in the N-terminal domain of transcription factor Nrf1 that control its orientation in the endoplasmic reticulum membrane.

The Biochemical Journal
Yiguo Zhang, John D Hayes

Abstract

Nrf1 [NF-E2 (nuclear factor-erythroid 2)-related factor 1] is a CNC (cap'n'collar) bZIP (basic-region leucine zipper) transcription factor that is tethered to ER (endoplasmic reticulum) and nuclear envelope membranes through its N-terminal signal peptide (residues 1-30). Besides the signal peptide, amino acids 31-90 of Nrf1 also negatively regulate the CNC-bZIP factor. In the present study we have tested the hypothesis that amino acids 31-90 of Nrf1, and the overlapping NHB2 (N-terminal homology box 2; residues 82-106), inhibit Nrf1 because they control its topology within membranes. This region contains three amphipathic alpha-helical regions comprising amino acids 31-50 [called the SAS (signal peptide-associated sequence)], 55-82 [called the CRACs (cholesterol-recognition amino acid consensus sequences)] and 89-106 (part of NHB2). We present experimental data showing that the signal peptide of Nrf1 contains a TM1 (transmembrane 1) region (residues 7-24) that is orientated across the ER membrane in an N(cyt)/C(lum) fashion with its N-terminus facing the cytoplasm and its C-terminus positioned in the lumen of the ER. Once Nrf1 is anchored to the ER membrane through TM1, the remaining portion of the N-terminal domain (NTD, resid...Continue Reading

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Citations

Sep 27, 2013·PLoS Genetics·Kira M Glover-CutterT Keith Blackwell
Jan 5, 2012·PloS One·Nikolai L ChepelevWilliam G Willmore
Apr 14, 2016·Indian Journal of Clinical Biochemistry : IJCB·Abbas Ali MahdiArshiya Parveen
May 2, 2017·Annual Review of Biochemistry·Ivan Dikic
Jun 27, 2018·Molecular and Cellular Biology·Hiroki SekineHozumi Motohashi
Jun 27, 2013·Cellular and Molecular Life Sciences : CMLS·Hadi DigalehFariba Khodagholi
Sep 15, 2020·Molecular Biology of the Cell·Amy NorthropSenthil K Radhakrishnan
Jan 18, 2020·International Journal of Molecular Sciences·Amy NorthropSenthil K Radhakrishnan
Feb 5, 2021·Cancers·Hiroki Sekine, Hozumi Motohashi
Oct 27, 2021·Journal of Biochemistry·Nicolas John Lehrbach

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