Condition‐dependent structural collapse in the intrinsically disordered N‐terminal domain of prion protein

IUBMB Life ◽  
2021 ◽  
Author(s):  
Eric H.‐L. Chen ◽  
Kuei‐Ming Lin ◽  
Jason C. Sang ◽  
Meng‐Ru Ho ◽  
Chih‐Hsuan Lee ◽  
...  
Keyword(s):  
Prion Protein ◽  
Structural Collapse ◽  
Intrinsically Disordered ◽  
Terminal Domain

Role of Prion Disease-Linked Mutations in the Intrinsically Disordered N-Terminal Domain of the Prion Protein

2013 ◽  
Vol 9 (11) ◽  
pp. 5158-5167 ◽  
Author(s):  
Xiaojing Cong ◽  
Nicola Casiraghi ◽  
Giulia Rossetti ◽  
Sandipan Mohanty ◽  
Gabriele Giachin ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Intrinsically Disordered ◽  
Terminal Domain

scholarly journals Alterations in the brain interactome of the intrinsically disordered N-terminal domain of the cellular prion protein (PrPC) in Alzheimer’s disease

PLoS ONE ◽  
2018 ◽  
Vol 13 (5) ◽  
pp. e0197659 ◽  
Author(s):  
Sarah Ulbrich ◽  
Petra Janning ◽  
Ralf Seidel ◽  
Jakob Matschke ◽  
Anika Gonsberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Prion Protein ◽  
Cellular Prion Protein ◽  
Intrinsically Disordered ◽  
Terminal Domain ◽  
The Brain

scholarly journals Biological Functions of the Intrinsically Disordered N-Terminal Domain of the Prion Protein: A Possible Role of Liquid–Liquid Phase Separation

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1201
Author(s):  
Stella A. Polido ◽  
Janine Kamps ◽  
Jörg Tatzelt
Keyword(s):  
Prion Protein ◽  
Tertiary Structure ◽  
Polypeptide Chain ◽  
Protein A ◽  
Interacting Proteins ◽  
Intrinsically Disordered ◽  
Terminal Domain ◽  
Protein Classes ◽  
Liquid Liquid Phase Separation

The mammalian prion protein (PrPC) is composed of a large intrinsically disordered N-terminal and a structured C-terminal domain, containing three alpha-helical regions and a short, two-stranded beta-sheet. Traditionally, the activity of a protein was linked to the ability of the polypeptide chain to adopt a stable secondary/tertiary structure. This concept has been extended when it became evident that intrinsically disordered domains (IDDs) can participate in a broad range of defined physiological activities and play a major functional role in several protein classes including transcription factors, scaffold proteins, and signaling molecules. This ability of IDDs to engage in a variety of supramolecular complexes may explain the large number of PrPC-interacting proteins described. Here, we summarize diverse physiological and pathophysiological activities that have been described for the unstructured N-terminal domain of PrPC. In particular, we focus on subdomains that have been conserved in evolution.

scholarly journals EGCG binds intrinsically disordered N-terminal domain of p53 and disrupts p53-MDM2 interaction

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Zhao ◽  
Alan Blayney ◽  
Xiaorong Liu ◽  
Lauren Gandy ◽  
Weihua Jin ◽  
...  
Keyword(s):  
Large Scale ◽  
Molecular Mechanisms ◽  
Epigallocatechin Gallate ◽  
Cancer Drug ◽  
Dynamic Interactions ◽  
Cancer Drug Discovery ◽  
Intrinsically Disordered ◽  
Terminal Domain ◽  
Cancerous Cells

AbstractEpigallocatechin gallate (EGCG) from green tea can induce apoptosis in cancerous cells, but the underlying molecular mechanisms remain poorly understood. Using SPR and NMR, here we report a direct, μM interaction between EGCG and the tumor suppressor p53 (KD = 1.6 ± 1.4 μM), with the disordered N-terminal domain (NTD) identified as the major binding site (KD = 4 ± 2 μM). Large scale atomistic simulations (>100 μs), SAXS and AUC demonstrate that EGCG-NTD interaction is dynamic and EGCG causes the emergence of a subpopulation of compact bound conformations. The EGCG-p53 interaction disrupts p53 interaction with its regulatory E3 ligase MDM2 and inhibits ubiquitination of p53 by MDM2 in an in vitro ubiquitination assay, likely stabilizing p53 for anti-tumor activity. Our work provides insights into the mechanisms for EGCG’s anticancer activity and identifies p53 NTD as a target for cancer drug discovery through dynamic interactions with small molecules.

scholarly journals Determinants of carboxyl-terminal domain translocation during prion protein biogenesis

1994 ◽  
Vol 269 (24) ◽  
pp. 16810-16820
Author(s):  
K.A. De Fea ◽  
D.H. Nakahara ◽  
M.C. Calayag ◽  
C.S. Yost ◽  
L.F. Mirels ◽  
...  
Keyword(s):  
Prion Protein ◽  
Terminal Domain ◽  
Carboxyl Terminal Domain ◽  
Protein Biogenesis ◽  
Carboxyl Terminal

scholarly journals Structural heterogeneity in the intrinsically disordered RNA polymerase II C-terminal domain

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Bede Portz ◽  
Feiyue Lu ◽  
Eric B. Gibbs ◽  
Joshua E. Mayfield ◽  
M. Rachel Mehaffey ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Structural Heterogeneity ◽  
Intrinsically Disordered ◽  
Terminal Domain

scholarly journals Improving the Performance of Simulations of the Intrinsically Disordered N-Terminal Domain from P53

2017 ◽  
Vol 112 (3) ◽  
pp. 207a-208a
Author(s):  
Nic A. Ezzell ◽  
Yue Zhang ◽  
Steven T. Whitten ◽  
Nicholas C. Fitzkee
Keyword(s):  
Intrinsically Disordered ◽  
Terminal Domain
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