A5029912085- Protein Structure and Dynamics
- Epigenetics and DNA Methylation
- Enzyme Structure and Function
- Chronic Lymphocytic Leukemia Research
- Immunodeficiency and Autoimmune Disorders
- Cancer-related gene regulation
- RNA modifications and cancer
- Cellular transport and secretion
- Protein Kinase Regulation and GTPase Signaling
- Amyloidosis: Diagnosis, Treatment, Outcomes
- RNA and protein synthesis mechanisms
- Galectins and Cancer Biology
- Glycosylation and Glycoproteins Research
- Mass Spectrometry Techniques and Applications
- Ubiquitin and proteasome pathways
- Signaling Pathways in Disease
- Monoclonal and Polyclonal Antibodies Research
- Bacteriophages and microbial interactions
- Kruppel-like factors research
- Genetics and Neurodevelopmental Disorders
- Pancreatitis Pathology and Treatment
- Nutrition, Genetics, and Disease
- Biochemical and Structural Characterization
- Protein Tyrosine Phosphatases
- Antimicrobial Peptides and Activities
National Taiwan University
2015-2025
National Yang Ming Chiao Tung University
2023
National Taiwan University Hospital
2023
Rutgers, The State University of New Jersey
2009-2016
Western University
2007
National Tsing Hua University
1996-2006
The cAMP-mediated allosteric transition in the catabolite activator protein (CAP; also known as cAMP receptor protein, CRP) is a textbook example of modulation DNA-binding activity by small-molecule binding. Here we report structure CAP absence cAMP, which, together with structures presence defines atomic details transition. structural changes, and their relationship to binding DNA binding, are remarkably clear simple. Binding results coil-to-helix that extends coiled-coil dimerization...
Significance Polyamines are small organic compounds that carry multiple positive charges at physiological pH. With a high capacity to interact with the acidic surface patches of proteins and nucleic acids, polyamines may regulate variety cellular processes, fluctuations in intracellular polyamine levels rigorously controlled during cell growth differentiation through interplay between enzyme ornithine decarboxylase (ODC) two regulatory proteins: antizyme (Az) inhibitor (AzIN). ODC initiates...
Abstract SMYD3 methyltransferase is nearly undetectable in normal human tissues but highly expressed several cancers, including breast cancer, although its contributions to pathogenesis this setting are unclear. Here we report that histone H2A.Z.1 a substrate of supports malignancy. SMYD3-mediated dimethylation at lysine 101 (H2A.Z.1K101me2) increased stability by preventing binding the removal chaperone ANP32E and facilitating interaction with H3. Moreover, microarray analysis identified...
Peptidoglycan (PG) is a highly cross-linked, protective mesh-like sacculus that surrounds the bacterial cytoplasmic membrane. Expansion of PG tightly coupled to growth cell and requires hydrolases cleave cross-links for insertion nascent material. In Escherichia coli, proteolytic system comprising periplasmic PDZ-protease Prc lipoprotein adaptor NlpI contributes enlargement by regulating cellular levels MepS, cross-link-specific hydrolase. Here, we demonstrate how binds facilitate...
Parkinson's disease is a neurodegenerative disorder with multifactorial aetiology. Nevertheless, the genetic predisposition in many families multi-incidence remains unknown. This study aimed to identify novel genes that cause familial disease. Whole exome sequencing was performed three affected members of index family late-onset autosomal-dominant parkinsonism and polyneuropathy. We identified heterozygous substitution c.941A>C (p.Tyr314Ser) mitochondrial ubiquinol-cytochrome c reductase...
Abstract Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a neurodegenerative disease caused by mutations in the gene encoding (TTR). Despite amyloid deposition being pathognomonic for diagnosis, this pathology nervous tissues cannot fully account nerve degeneration, implying additional pathophysiology neurodegeneration, which, however, has not yet been elucidated. In study, neuroinflammation ATTRv-PN was investigated examining morphometry, blood-nerve barrier, and...
Significance It is known that nutrient starvation stimulates mitochondrial fusion for cell survival. In this study, a homozygous mutation in the NME3 gene, which encodes an NDP kinase, was identified fatal neurodegenerative disorder. Cells derived from patient were deficient of and intolerant to glucose starvation. Patient cells used demonstrate rescued survival by two separate functions, namely stimulation kinase activity. Since dynamics energy efficiency are important neuronal development,...
ABSTRACT Trp-rich antimicrobial peptides play important roles in the host innate defense mechanisms of many plants, insects, and mammals. A new type peptide, Ac-KWRRWVRWI-NH 2 , designated Pac-525, was found to possess improved activity against both gram-positive -negative bacteria. We have determined that solution structures Pac-525 bound membrane-mimetic sodium dodecyl sulfate (SDS) micelles. The SDS micelle-bound structure adopts an α-helical segment at residues Trp2, Arg3, Arg4....
Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks have constituted a public health issue with drastic mortality higher than 34%, necessitating the development of an effective vaccine. During MERS-CoV infection, trimeric spike protein on viral envelope is primarily responsible for attachment to host cellular receptor, dipeptidyl peptidase 4 (DPP4). With goal generating protein-based prophylactic, we designed subunit vaccine comprising recombinant S1 trimerization motif (S1-Fd)...
Abstract Objectives Hereditary transthyretin (TTR) amyloidosis (ATTRv) is frequently complicated by polyneuropathy (ATTRv‐PN) and cardiomyopathy (ATTRv‐CM). The long‐term efficacy of diflunisal on both in ATTRv patients, especially those with non‐V30M genotypes, has not been fully investigated compared that tafamidis. Methods We the structural biochemical characteristics A97S‐TTR complexed tafamidis diflunisal, prospectively followed up progression between ATTRv‐PN patients taking Results...
Transthyretin (TTR)-related amyloidosis (ATTR) is a syndrome of diseases characterized by the extracellular deposition fibrillar materials containing TTR variants. Ala97Ser (A97S) major mutation reported in Taiwanese ATTR patients. Here, we combine atomic resolution structural information together with biochemical data to demonstrate that substitution polar Ser for small hydrophobic side chain Ala at residue 97 largely influences local packing density FG-loop, thus leading conformational...
The Lon AAA+ protease (LonA) is a ubiquitous ATP-dependent proteolytic machine, which selectively degrades damaged proteins or native carrying exposed motifs (degrons). Here we characterize the structural basis for substrate recognition and discrimination by N-terminal domain (NTD) of LonA. results reveal that six NTDs are attached to hexameric LonA chamber flexible linkers such formers tumble independently latter. Further spectral analyses show NTD interacts with unfolded proteins, protein...
Abstract X‐linked agammaglobulinemia (XLA) is caused by mutations in the Bruton's tyrosine kinase (Btk). The absence of functional Btk leads to failure B‐cell development that incapacitates antibody production XLA patients leading recurrent bacterial infections. SH2 domain essential for phospholipase C‐γ phosphorylation, and this were shown cause XLA. Recently, linker protein (BLNK) was found interact with Btk, association required activation C‐γ. However, molecular basis interaction between...
Increasing evidence suggests that gut microbiota alterations are related to development and phenotypes of many neuropsychiatric diseases. Here, we evaluated the fecal its clinical correlates in patients with hereditary transthyretin amyloidosis (ATTRv) polyneuropathy. Fecal from 38 ATTRv 39 age-matched controls was analyzed by sequencing 16S V3-V4 ribosomal RNA, relationships characteristics polyneuropathy cardiomyopathy were explored. The familial amyloidotic stage I, II, III 13, 18, 7...
Abstract Peptidoglycan (PG) sacculi surround the cytoplasmic membrane, maintaining cell integrity by withstanding internal turgor pressure. During growth, PG endopeptidases cleave crosslinks of fully closed sacculi, allowing for incorporation new glycan strands and expansion peptidoglycan mesh. Outer-membrane-anchored NlpI associates with hydrolases synthases near synthesis complexes, facilitating spatially close hydrolysis. Here, we present structure adaptor in complex endopeptidase MepS,...
Bruton's tyrosine kinase (BTK) plays an important role in B cell development. Deletion of C-terminal 14 amino acids the SH3 domain BTK results X-linked agammaglobulinemia (XLA), inherited disease. We report here on stability and folding BTK. Peptides corresponding to residues 216-273 (58 residues) 216-259 (44 were synthesized by solid phase methods; first peptide constitutes entire while latter lacks acid C-terminal. The 58 forms mainly a beta-barrel type unit. Although small lacking...