A5048271521- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Machine Learning in Bioinformatics
- Vibrio bacteria research studies
- Genomics and Phylogenetic Studies
- Renal cell carcinoma treatment
- Renal and related cancers
- Polyamine Metabolism and Applications
- Cellular transport and secretion
- Autophagy in Disease and Therapy
- PI3K/AKT/mTOR signaling in cancer
- Escherichia coli research studies
- Genetic and Kidney Cyst Diseases
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Ubiquitin and proteasome pathways
- Biochemical and Molecular Research
- Aquaculture disease management and microbiota
- Glycosylation and Glycoproteins Research
- Amino Acid Enzymes and Metabolism
- Computational Drug Discovery Methods
- Endoplasmic Reticulum Stress and Disease
- Trypanosoma species research and implications
- RNA modifications and cancer
Howard Hughes Medical Institute
2015-2024
The University of Texas Southwestern Medical Center
2015-2024
Southwestern Medical Center
2008-2024
University of South Alabama
2024
University of Maine
2024
University of California, San Diego
2015
Center for Cancer Research
2013
Frederick National Laboratory for Cancer Research
2013
The University of Texas Health Science Center at San Antonio
2013
Science Applications International Corporation (United States)
2013
Deep learning takes on protein folding In 1972, Anfinsen won a Nobel prize for demonstrating connection between protein’s amino acid sequence and its three-dimensional structure. Since 1994, scientists have competed in the biannual Critical Assessment of Structure Prediction (CASP) protein-folding challenge. methods took center stage at CASP14, with DeepMind’s Alphafold2 achieving remarkable accuracy. Baek et al . explored network architectures based DeepMind framework. They used three-track...
Obesity and insulin resistance are associated with deposition of triglycerides in tissues other than adipose tissue. Previously, we showed that a missense mutation (I148M) PNPLA3 (patatin-like phospholipase domain-containing 3 protein) is increased hepatic triglyceride content humans. Here examined the effect I148M substitution on enzymatic activity cellular location PNPLA3. Structural modeling predicted methionine for isoleucine at residue 148 would restrict access substrate to catalytic...
Abstract We describe predictions made using the Rosetta structure prediction methodology for Eighth Critical Assessment of Techniques Protein Structure Prediction. Aggressive sampling and all‐atom refinement were carried out nearly all targets. A combination alignment methodologies was used to generate starting models from a range templates, then subjected atom refinement. For 64 domains with readily identified best submitted model better than template in Data Bank 24 cases, improved over 43...
Protein phosphorylation is a fundamental mechanism regulating nearly every aspect of cellular life. Several secreted proteins are phosphorylated, but the kinases responsible unknown. We identified family atypical protein that localize within Golgi apparatus and secreted. Fam20C appears to be casein kinase phosphorylates secretory pathway S-x-E motifs. caseins several implicated in biomineralization, including small integrin-binding ligand, N-linked glycoproteins (SIBLINGs). Consequently,...
Understanding the evolution of a protein, including both close and distant relationships, often reveals insight into its structure function. Fast easy access to such up-to-date information facilitates research. We have developed hierarchical evolutionary classification all proteins with experimentally determined spatial structures, presented it as an interactive updatable online database. ECOD (Evolutionary Classification protein Domains) is distinct from other structural classifications in...
Cellular iron homeostasis is maintained by the coordinate posttranscriptional regulation of genes responsible for uptake, release, use, and storage through actions regulatory proteins IRP1 IRP2. However, manner in which levels are sensed to affect IRP2 activity poorly understood. We found that an E3 ubiquitin ligase complex containing FBXL5 protein targets proteasomal degradation. The stability itself was regulated, accumulating under iron- oxygen-replete conditions degraded upon depletion....
The Vibrio parahaemolyticus type III effector VopS is implicated in cell rounding and the collapse of actin cytoskeleton by inhibiting Rho guanosine triphosphatases (GTPases). We found that could act to covalently modify a conserved threonine residue on Rho, Rac, Cdc42 with adenosine 5'-monophosphate (AMP). resulting AMPylation prevented interaction GTPases downstream effectors, thereby assembly infected cell. Eukaryotic proteins were also directly modified AMP, potentially expanding...
The prediction of the structures proteins without detectable sequence similarity to any protein known structure remains an outstanding scientific challenge. Here we report significant progress in this area. We first describe de novo blind predictions unprecendented accuracy made for two large families recent CASP11 test methods by incorporating residue–residue co-evolution information Rosetta program. then use method generate models 58 121 prokaryotes which three-dimensional are not...
The catalytic engine of RNA interference (RNAi) is the RNA-induced silencing complex (RISC), wherein endoribonuclease Argonaute and single-stranded small interfering (siRNA) direct target mRNA cleavage. We reconstituted long double-stranded RNA- duplex siRNA-initiated RISC activities with use recombinant Drosophila Dicer-2, R2D2, Ago2 proteins. used this core reconstitution system to purify an RNAi regulator that we term C3PO (component 3 promoter RISC), a Translin Trax. Mg2+-dependent...
Defects in Niemann-Pick, Type C-1 protein (NPC1) cause cholesterol, sphingolipids, phospholipids, and glycolipids to accumulate lysosomes of liver, spleen, brain. In cultured fibroblasts, NPC1 deficiency causes lysosomal retention lipoprotein-derived cholesterol after uptake by receptor-mediated endocytosis. contains 1278 amino acids that form 13 membrane-spanning helices three large loops project into the lumen lysosomes. We showed earlier binds oxysterols. Here we localize binding site...
Significance The recently discovered type VI secretion system (T6SS) is used by Gram-negative bacteria to deliver effector proteins into both eukaryotic and prokaryotic neighboring cells mediate virulence competition, respectively. Even though several T6SS families have been described, many T6SSs are not associated with known effectors. In this work, we report the discovery of a conserved motif named MIX (marker for six effectors) that often located near genome neighborhood found in numerous...
Abstract Renal cell carcinoma (RCC) clusters in some families. Familial RCC arises from mutations several genes, including the von Hippel-Lindau (VHL) tumor suppressor, which is also mutated sporadic RCC. However, a significant percentage of familial remains unexplained. Recently, we discovered that BRCA1-associated protein-1 (BAP1) gene The BAP1 encodes nuclear deubiquitinase and appears to be classic two-hit suppressor gene. Somatic are associated with high-grade, clear-cell (ccRCC) poor...
Acute hepatopancreatic necrosis disease (AHPND) is a newly emerging shrimp that has severely damaged the global industry. AHPND caused by toxic strains of Vibrio parahaemolyticus have acquired "selfish plasmid" encoding deadly binary toxins PirAvp/PirBvp To better understand repertoire virulence factors in AHPND-causing V. parahaemolyticus, we conducted comparative analysis using genome sequences clinical strain RIMD2210633 and environmental non-AHPND isolates Interestingly, found all...