THE METASTABILITY OF PROTEOME FOLDEDNESS IN NEURODEGENERATIVE DISEASE

Arginine-rich C9ORF72 ALS proteins stall ribosomes in a manner distinct from a canonical ribosome-associated quality control substrate.

Viacheslav Kriachkov, Angelique R Ormsby, Eric P Kusnadi, Hamish EG McWilliam, Justine D Mintern, Shanika L Amarasinghe, Matthew E Ritchie, Luc Furic, Danny M Hatters

2023-01-01

Hexanucleotide expansion mutations in C9ORF72 are a frequent cause of amyotrophic lateral sclerosis. We previously reported that l..

Protein painting reveals pervasive remodeling of conserved proteostasis machinery in response to pharmacological stimuli

Dezerae Cox, Angelique R Ormsby, Gavin E Reid, Danny M Hatters

2022-11-28

The correct spatio-temporal organization of the proteome is essential for cellular homeostasis. However, a detailed mechanistic un..

Sequence grammar underlying the unfolding and phase separation of globular proteins

Kiersten M Ruff, Yoon Hee Choi, Dezerae Cox, Angelique R Ormsby, Yoochan Myung, David B Ascher, Sheena E Radford, Rohit V. Pappu, Danny M Hatters

2022-09-01

Aberrant phase separation of globular proteins is associated with many diseases. Here, we use a model protein system to understand..

A Census of Hsp70-Mediated Proteome Solubility Changes upon Recovery from Heat Stress

Xiaojing Sui, Dezerae Cox, Shuai Nie, Gavin E Reid, Danny M Hatters

2022-05-06

Eukaryotic cells respond to heat shock through several regulatory processes including upregulation of stress responsive chaperones..

Hidden information on protein function in censuses of proteome foldedness

Dezerae Cox, Ching-Seng Ang, Nadinath B Nillegoda, Gavin E Reid, Danny M Hatters

2022-04-14

Methods that assay protein foldedness with proteomics have generated censuses of apparent protein folding stabilities in biologica..

Development and application of Diels-Alder adducts displaying AIE properties

Timothy L Gialelis, Tze Cin Owyong, Siyang Ding, Wenyi Li, Maoxing Yu, Neil M O'Brien-Simpson, Zujin Zhao, Jonathan M White, Bicheng Yao, Yuning Hong

2022-02-16

Exploring organic reactions to construct novel molecules with aggregation-induced emission (AIE) features is an essential branch o..

Flipping the switch: How cysteine oxidation directs tau amyloid conformations

Danny M Hatters

2021-11-01

Tau can adopt distinct fibril conformations in different human neurodegenerative diseases, which may invoke distinct pathological ..

Recent advances in bioanalytical methods to measure proteome stability in cells

Shouxiang Zhang, David W Greening, Yuning Hong

2021-04-07

Proteome stability constitutes an essential aspect of protein homeostasis (proteostasis). Proteostasis networks maintain proteins ..

Immiscible inclusion bodies formed by polyglutamine and poly(glycine-alanine) are enriched with distinct proteomes but converge in proteins that are risk factors for disease and involved in protein degradation

Mona Radwan, Jordan D Lilley, Ching-Seng Ang, Gavin E Reid, Danny M Hatters

2020-08-28

Poly(glycine-alanine) (polyGA) is one of the polydipeptides expressed in Frontotemporal Dementia and/or Amyotrophic Lateral Sclero..

Nascent mutant Huntingtin exon 1 chains do not stall on ribosomes during translation but aggregates do recruit machinery involved in ribosome quality control and RNA

Angelique R Ormsby, Dezerae Cox, James Daly, David Priest, Elizabeth Hinde, Danny M Hatters

2020-07-31

Mutations that cause Huntington's Disease involve a polyglutamine (polyQ) sequence expansion beyond 35 repeats in exon 1 of Huntin..

A Molecular Chameleon for Mapping Subcellular Polarity in an Unfolded Proteome Environment

Tze Cin Owyong, Pramod Subedi, Jieru Deng, Elizabeth Hinde, Jason J Paxman, Jonathan M White, Weisan Chen, Begona Heras, Wallace WH Wong, Yuning Hong

2020-06-15

Environmental polarity is an important factor that drives biomolecular interactions to regulate cell function. Herein, a general m..

A Molecular Chameleon for Mapping Subcellular Polarity in an Unfolded Proteome Environment

Tze Cin Owyong, Pramod Subedi, Jieru Deng, Elizabeth Hinde, Jason J Paxman, Jonathan M White, Weisan Chen, Begoña Heras, Wallace WH Wong, Yuning Hong

2020-06-15

Arginine in C9ORF72 Dipolypeptides Mediates Promiscuous Proteome Binding and Multiple Modes of Toxicity

Mona Radwan, Ching-Seng Ang, Angelique R Ormsby, Dezerae Cox, James C Daly, Gavin E Reid, Danny M Hatters

2020-04-01

C9ORF72-associated Motor Neuron Disease patients feature abnormal expression of 5 dipeptide repeat (DPR) polymers. Here we used qu..

Widespread remodeling of proteome solubility in response to different protein homeostasis stresses

Xiaojing Sui, Douglas EV Pires, Angelique R Ormsby, Dezerae Cox, Shuai Nie, Giulia Vecchi, Michele Vendruscolo, David B Ascher, Gavin E Reid, Danny M Hatters

2020-02-04

The accumulation of protein deposits in neurodegenerative diseases has been hypothesized to depend on a metastable subproteome vul..

Modest Declines in Proteome Quality Impair Hematopoietic Stem Cell Self-Renewal

Lorena Hidalgo San Jose, Mary Jean Sunshine, Christopher H Dillingham, Bernadette A Chua, Miriama Kruta, Yuning Hong, Danny M Hatters, Robert AJ Signer

2020-01-07

Low protein synthesis is a feature of somatic stem cells that promotes regeneration in multiple tissues. Modest increases in prote..