A5081917442- Microtubule and mitosis dynamics
- Protein Structure and Dynamics
- Photosynthetic Processes and Mechanisms
- RNA and protein synthesis mechanisms
- Cellular transport and secretion
- RNA Research and Splicing
- Enzyme Structure and Function
- Protist diversity and phylogeny
- RNA modifications and cancer
- Glycosylation and Glycoproteins Research
- 14-3-3 protein interactions
- Redox biology and oxidative stress
- Biochemical effects in animals
- Advanced MRI Techniques and Applications
- Advanced Electron Microscopy Techniques and Applications
- thermodynamics and calorimetric analyses
- Viral Infections and Immunology Research
- Electron Spin Resonance Studies
- Monoclonal and Polyclonal Antibodies Research
- CRISPR and Genetic Engineering
- Mitochondrial Function and Pathology
- Cancer-related gene regulation
- Biochemical and Structural Characterization
- Chromosomal and Genetic Variations
- Genomics and Phylogenetic Studies
Oregon State University
2016-2025
Corvallis Environmental Center
2013-2021
ORCID
2018
Institute of Molecular Biology and Biophysics
2009
University of Minnesota
1995-2006
Ohio University
1999-2006
Oregon Health & Science University
1996
Portland State University
1992-1996
The operations within a living cell depend on the collective activity of networks proteins, sometimes termed "interactomes". Within these networks, most proteins interact with few partners, while small proportion called hubs, participate in large number interactions and play central role organizing interactomes. LC8 was first discovered as an essential component microtubule-based molecular motor dynein such is involved fundamental processes, including retrograde vesicular trafficking,...
The nucleocapsid protein (N) of SARS-CoV-2 is essential for virus replication, genome packaging, evading host immunity, and maturation. N a multidomain composed an independently folded monomeric N-terminal domain that the primary site RNA binding, dimeric C-terminal efficient phase separation condensate formation with RNA. domains are separated by disordered Ser/Arg-rich region preceding self-associating Leu-rich helix. Phosphorylation in Ser/Arg infected cells decreases viscosity N:RNA...
Hydroxyproline (Hyp) O-glycosylation characterizes the hydroxyproline-rich glycoprotein (HRGP) superfamily of plant extracellular matrix. Hyp glycosylation occurs in two modes: Arabinosylation adds short oligoarabinosides (Hyp-arabinosides) while galactosylation leads to addition larger arabinogalactan polysaccharides (Hyp-polysaccharides). We hypothesize that sequence-dependent small peptide motifs results glycomodules. These functional units combination with other repetitive modules define...
Nuclear pore complexes (NPCs) are huge assemblies formed from ∼30 different nucleoporins, typically organized in subcomplexes. One module, the conserved Nup82 complex at cytoplasmic face of NPCs, is crucial to terminate mRNA export. To gain insight into structure, assembly, and function filaments, we reconstituted yeast Nup82–Nup159–Nsp1–Dyn2 complex, which was suitable for biochemical, biophysical, electron microscopy analyses. Our integrative approach revealed that forms an unusual...
The interactions of three subunits cytoplasmic dynein from Drosophila melanogaster, LC8, Tctex-1, and the N-terminal domain IC74 (N-IC74, residues 1−289), were characterized in vitro by affinity methods, limited proteolysis, circular dichroism spectroscopy. These chosen for study because they are presumed to promote assembly complex be engaged controlled binding release cargo. Limited proteolysis mass spectrometry N-IC74 presence LC8 Tctex-1 localized vicinity K104 K105, region downstream...
Dynein light chains are thought to increase binding efficiency of dynein intermediate chain both heavy and dynactin, but their exact role is not clear. Isothermal titration calorimetry x-ray crystallography reported herein indicate that multivalency effects underlie efficient assembly regulation. For a ternary complex 60-amino acid segment (IC) bound two homodimeric Tctex1 LC8, there 50-fold affinity enhancement for the second binding. designed IC construct containing LC8 sites, observed...
In animal gonads, the PIWI-interacting RNA (piRNA) pathway guards genome integrity in part through co-transcriptional gene silencing of transposon insertions.
Abstract The nucleocapsid (N) protein of SARS-CoV-2 binds viral RNA, condensing it inside the virion, and phase separating with RNA to form liquid–liquid condensates. There is little consensus on what differentiates sequence-independent N–RNA interactions in virion or liquid droplets from those specific genomic (gRNA) motifs necessary for function infected cells. To identify structures N domains responsible separation, we use first 1,000 nt short segments designed as models single-stranded...
Eukaryotic ribosome biogenesis involves ∼200 assembly factors, but how these contribute to maturation is poorly understood. Here, we identify a network of factors on the nascent 60S subunit that actively remodels preribosome structure. At its hub Rsa4, direct substrate force-generating ATPase Rea1. We show Rsa4 connected central protuberance by binding Rpl5 and ribosomal RNA (rRNA) helix 89 peptidyl transferase center (PTC) through Nsa2. Importantly, Nsa2 binds before relocation PTC....
The transcription factor ASCIZ (ATMIN, ZNF822) has an unusually high number of recognition motifs for the product its main target gene, hub protein LC8 (DYNLL1). Using a combination biophysical methods, structural analysis by NMR and electron microscopy, cellular assays, we developed model that proposes concerted role intrinsic disorder multiple binding events in regulating transcription. We demonstrate long intrinsically disordered C-terminal domain binds to form dynamic ensemble complexes...
Pyrenophora tritici-repentis Ptr ToxB (ToxB) is a proteinaceous host-selective toxin produced by (P. tritici-repentis), plant pathogenic fungus that causes the disease tan spot of wheat. One feature distinguishes from other toxins it has naturally occurring homologs in non-pathogenic P. isolates lack toxic activity. There are no high-resolution structures for any homologs, or protein with >30% sequence identity, and therefore what underlies activity remains an open question. Here, we present...
Deamidation is a major age-related modification in the human lens that highly prevalent crystallins isolated from insoluble fraction of cataractous lenses and also causes protein aggregation vitro. However, mechanism by which deamidation proteins to become not known because only subtle structural changes were observed We have identified Asn14 Asn76 γS-crystallin as deamidated aged lenses. These sites are on surface N-terminal domain mimicked replacing Asn with Asp residues order generate...
Hub proteins participate in cellular regulation by dynamic binding of multiple within interaction networks. The hub protein LC8 reversibly interacts with more than 100 partners through a flexible pocket at its dimer interface. To explore the diversity partner pool, we screened for using proteomic phage display library composed peptides from human proteome, which had no bias toward known motif. Of identified hits, validated 29 isothermal titration calorimetry. peptides, 19 were entirely...