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Articles by Eric Tse
De novo design of semisynthetic conduction pores
Abstract Protein pores used for molecular sensing are generally assembled from large, multi-subunit natural proteins. Their ion conductance, and thus performance in sensing applications, depends on lumen geometry and chemistry. Here rather than designing a new pore or relying only on mutations to a natural scaffold, we show that installing additional de novo subunits to native protein pore complexes enables large-scale architectural changes.
CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis
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Keywords neurodegeneration proteostasis protein aggregation tau CRISPR screen CUL5 SOCS4 Introduction Tauopathies, which include Alzheimer’s disease (AD), are neurodegenerative diseases that are defined by aggregation of the protein tau and that are lacking effective therapeutics. Tau is an intrinsically disordered protein, and its canonical function is to regulate the stability and dynamics of microtubules.
By Avi J. Samelson, Nabeela Ariqat, Justin M. McKetney, Gita Rohanitazangi, Celeste Parra Bravo, Rudra Bose, Kyle J. Travaglini, Victor Lam, Darrin Goodness, Thomas TA, Gary Dixon Verified, Emily Marzette, Julianne Jin, Ruilin Tian, Eric Tse, Romany N. N. Abskharon, Henry Pan, Emma Carroll, Rosalie E. Lawrence, Jason E. Gestwicki, Jessica Rexach, David Eisenberg, Nicholas M. Kanaan, Daniel R. Southworth, Danielle L. Swaney, Martin Kampmann
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Cell Press
Verified
Emerging therapeutic strategies for mature T-cell and natural killer-cell lymphomas
Get full text access Log in, subscribe or purchase for full access. References 1. Lim, MS ∙ Chan, JKC ∙ de Jong, D ∙ et al. T-cell and NK-cell lymphoid proliferations and lymphomas WHO Classification of Tumours Editorial Board (Editor) Haematolymphoid tumours, WHO classifications of tumours International Agency for Research on Cancer, World Health Organization, 2024; 637-642 2. Chen, JJ ∙ Tokumori, FC ∙ Del Guzzo, C ∙ et al. Update on T-cell lymphoma epidemiology Curr Hematol Malig Rep.
OpenAI’s block in Hong Kong and mainland China deepens China-US divide
After OpenAI blocks access to its application programme interfaces (APIs) for Hong Kong and mainland China, startups and large corporations alike would plan on splitting their consumer markets into two camps. Hong Kong commentator Eric Tse discusses the issue. OpenAI, the developer of ChatGPT, announced that from 9 July, it would stop providing application programme interface (API) services to Hong Kong, mainland China, and other “unsupported countries and regions”.
Structure of a novel α-synuclein filament fold from multiple system atrophy
Abstract Multiple system atrophy (MSA) is a synucleinopathy, a group of related diseases characterized by the accumulation of α-synuclein aggregates in the brain. In MSA, these aggregates form glial cytoplasmic inclusions, which contain abundant cross-β amyloid filaments.
Asymmetric apical domain states of mitochondrial Hsp60 coordinate substrate engagement and chaperonin assembly - Nature Structural & Molecular Biology
Abstract The mitochondrial chaperonin, mitochondrial heat shock protein 60 (mtHsp60), promotes the folding of newly imported and transiently misfolded proteins in the mitochondrial matrix, assisted by its co-chaperone mtHsp10. Despite its essential role in mitochondrial proteostasis, structural insights into how this chaperonin progresses through its ATP-dependent client folding cycle are not clear.
Metal-detection based techniques and their applications for metallobiology
Metal-detection based techniques and their applications for metallobiology Metals are essential for human health and play a crucial role in numerous biological processes. Gaining a deeper insight into the metal-involved biological events will facilitate novel strategies for disease prevention, early detection, and personalized treatments.
Amyloid Accelerator Polyphosphate Implicated as the Mystery Density in α-Synuclein Fibrils
Abstract Aberrant aggregation of α-Synuclein is the pathological hallmark of a set of neurodegenerative diseases termed synucleinopathies. Recent advances in cryo-electron microscopy have led to the structural determination of the first synucleinopathy-derived α-Synuclein fibrils, which contain a non-proteinaceous, "mystery density" at the core of the protofilaments, hypothesized to be highly negatively charged.
Cryo-EM Structures Reveal Tau Filaments from Down Syndrome Adopt Alzheimer's Disease Fold
Abstract Down Syndrome (DS) is a common genetic condition caused by trisomy of chromosome 21. Among the complex clinical features including musculoskeletal, neurological and cardiovascular disabilities, individuals with DS develop progressive dementia and early onset Alzheimer's Disease (AD).
The p97/VCP adaptor UBXD1 drives AAA+ remodeling and ring opening through multi-domain tethered interactions - Nature Structural & Molecular Biology
Abstract p97, also known as valosin-containing protein, is an essential cytosolic AAA+ (ATPases associated with diverse cellular activities) hexamer that unfolds substrate polypeptides to support protein homeostasis and macromolecular disassembly. Distinct sets of p97 adaptors guide cellular functions but their roles in direct control of the hexamer are unclear.
Stacked binding of a PET ligand to Alzheimer’s tau paired helical filaments - Nature Communications
Abstract Accumulation of filamentous aggregates of tau protein in the brain is a pathological hallmark of Alzheimer’s disease (AD) and many other neurodegenerative tauopathies. The filaments adopt disease-specific cross-β amyloid conformations that self-propagate and are implicated in neuronal loss. Development of molecular diagnostics and therapeutics is of critical importance. However, mechanisms of small molecule binding to the amyloid core is poorly understood.
The p97/VCP adapter UBXD1 drives AAA+ remodeling and ring opening through multi-domain tethered interactions
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Asymmetric apical domain states of mitochondrial Hsp60 coordinate substrate engagement and chaperonin assembly
New Results doi: https://doi.org/10.1101/2023.05.15.540872 Abstract The mitochondrial chaperonin, mtHsp60, promotes the folding of newly imported and transiently misfolded proteins in the mitochondrial matrix, assisted by its co-chaperone mtHsp10. Despite its essential role in mitochondrial proteostasis, structural insights into how this chaperonin binds to clients and progresses through its ATP-dependent reaction cycle are not clear.
Correction to: Whole-genome sequencing identifies responders to Pembrolizumab in relapse/refractory natural-killer/T cell lymphoma
Correction to: Leukemia The authors did not declare a relevant conflict of interest thus wish to publish a correction to add this: Author information Author notes These authors contributed equally: Jing Quan Lim, Dachuan Huang, Tiffany Tang, Daryl Tan These authors jointly supervised this work: Jin-Xin Bei, Tongyu Lin, Choon Kiat Ong, Soon Thye Lim Affiliations State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer...
Whole-genome sequencing identifies responders to Pembrolizumab in relapse/refractory natural-killer/T cell lymphoma
To the Editor: Antibodies targeting the immune checkpoint axis have been approved by the FDA for the treatment of a broad range of malignancies [1]. NKTCL is an aggressive hematological malignancy derived from NK or T cells with ubiquitous Epstein–Barr virus (EBV) infection, and there is no standard therapeutic option established for patients with relapse/refractory (RR) NKTCL.
Oral arsenic trioxide, all‐trans retinoic acid, and ascorbic acid maintenance after first complete remission in acute promyelocytic leukemia: Long‐term results and unique prognostic indicators
Original Article Yok‐Lam Kwong MD Corresponding Author E-mail address: ylkwong@hkucc.hku.hk https://orcid.org/0000-0001-8156-6978 Department of Medicine, University of Hong Kong, Hong Kong, China Corresponding Author: Yok‐Lam Kwong, MD, Department of Medicine, Queen Mary Hospital, Pokfulam Road, Hong Kong, China (E-mail address: ylkwong@hkucc.hku.hk).
Conformational plasticity of the ClpAP AAA+ protease couples protein unfolding and proteolysis
Abstract The ClpAP complex is a conserved bacterial protease that unfolds and degrades proteins targeted for destruction. The ClpA double-ring hexamer powers substrate unfolding and translocation into the ClpP proteolytic chamber. Here, we determined high-resolution structures of wild-type Escherichia coli ClpAP undergoing active substrate unfolding and proteolysis. A spiral of pore loop–substrate contacts spans both ClpA AAA+ domains.
Competing protein-protein interactions regulate binding of Hsp27 to its client protein tau
Because the ACD has been shown to have chaperone activity for some clients20, we first measured the interaction of 15N-labeled Hsp27 ACD with tau by HSQC NMR11. In this experiment, we utilized two isoforms of tau (Fig. 1a and Supplementary Figure 1): the full-length splice variant 0N4R tau, which is commonly expressed in adult brain and K18, a construct containing just the four microtubule-binding repeats (MTBRs) that is known to contain the binding sites of other chaperones34,35.
X-linked inhibitor of apoptosis protein (XIAP) is a client of heat shock protein 70 (Hsp70) and a biomarker of its inhibition
Heat shock protein 70 (Hsp70) and Hsp90 are molecular chaperones that play essential roles in tumor growth by stabilizing pro-survival client proteins. However, although the development of Hsp90 inhibitors has benefited from the identification of clients, such as Raf-1 proto-oncogene, Ser/Thr kinase (RAF1), that are particularly dependent on this chaperone, no equivalent clients for Hsp70 have been reported.
X-Linked Inhibitor of Apoptosis Protein (XIAP) is a Client of Heat Shock Protein 70 (Hsp70) and a Biomarker of its Inhibition
X-Linked Inhibitor of Apoptosis Protein (XIAP) is a Client of Heat Shock Protein 70 (Hsp70) and a Biomarker of its Inhibition
X-Linked Inhibitor of Apoptosis Protein (XIAP) is a Client of Heat Shock Protein 70 (Hsp70) and a Biomarker of its Inhibition
Heat shock protein 70 (Hsp70) and Hsp90 are molecular chaperones that play essential roles in tumor growth by stabilizing pro-survival client proteins. However, while the development of Hsp90 inhibitors has benefited from the identification of clients, such as Raf-1 proto-oncogene, Ser/Thr kinase (RAF1), that are particularly dependent on this chaperone, no equivalent clients for Hsp70 have been reported.
Diagnosis and management of extranodal NK/T cell lymphoma nasal type
Introduction: Extranodal NK/T-cell lymphoma nasal type is a distinct clinicopathologic entity. The most common initial site of presentation is the nasopharyngeal area, but non-nasals sites including the skin and the gastrointestinal tract may be affected. Areas covered: The diagnosis and management of NK/T-cell lymphoma is discussed, based on a literature search on PubMed.
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