A5002286396- Heat shock proteins research
- Protein Structure and Dynamics
- Enzyme Structure and Function
- RNA modifications and cancer
- MicroRNA in disease regulation
- RNA Research and Splicing
- Monoclonal and Polyclonal Antibodies Research
- Endoplasmic Reticulum Stress and Disease
- Bacteriophages and microbial interactions
- RNA Interference and Gene Delivery
- HIV Research and Treatment
- RNA and protein synthesis mechanisms
- Computational Drug Discovery Methods
- Immune Cell Function and Interaction
- Ubiquitin and proteasome pathways
- Tea Polyphenols and Effects
- Systemic Lupus Erythematosus Research
- Pancreatic function and diabetes
- Cancer-related Molecular Pathways
- Advanced biosensing and bioanalysis techniques
- Clostridium difficile and Clostridium perfringens research
- Heme Oxygenase-1 and Carbon Monoxide
- Protease and Inhibitor Mechanisms
- Phosphodiesterase function and regulation
- vaccines and immunoinformatics approaches
The Ohio State University
2022-2024
Miami University
2014-2022
University of Michigan
2019-2020
Chinese Academy of Sciences
2013-2015
Shanghai Institute of Materia Medica
2015
Second Military Medical University
2010-2013
Huashan Hospital
2006
Fudan University
2006
MicroRNAs (miRNAs) are about 22-nucleotide (nt) noncoding RNAs forming the effector complexes with Argonaute (AGO) proteins to repress gene expression. Although tiny (tyRNAs) shorter than 19 nt have been found bind plant and vertebrate AGOs, their biogenesis remains a long-standing question. Here, our in vivo vitro studies show several 3′→5′ exonucleases, such as interferon-stimulated 20 kDa (ISG20), three prime repair exonuclease 1 (TREX1), ERI1 (enhanced RNAi, also known 3′hExo), capable...
Proteotoxicity from insufficient clearance of misfolded/damaged proteins underlies many diseases. Carboxyl terminus Hsc70-interacting protein (CHIP) is an important regulator proteostasis in cells, having E3-ligase and chaperone functions often directing damaged towards proteasome recycling. While enhancing CHIP functionality has broad therapeutic potential, prior efforts have all relied on genetic upregulation. Here we report that CHIP-mediated turnover markedly post-translationally...
Heat-shock protein 90 (Hsp90) is one of the most important chaperones involved in multiple cellular processes. The chaperoning function Hsp90 intimately coupled to ATPase activity presented by its N-terminal domain. However, molecular mechanism for ATP-dependent working cycle still not fully understood. In this study, we use NMR techniques investigate structural characteristics and dynamic behaviors domain free AMPPCP (ATP analogue) or ADP-bound states. We demonstrated that although ADP bind...
Detection of specific antibodies against hepatitis C virus (HCV) is the most widely available test for viral diagnosis and monitoring HCV infections. However, narrowing serologic window anti-HCV detection by enhancing IgM has remained to be a problem. Herein, we used LD5, novel evolved immunoglobulin-binding molecule (NEIBM) with high affinity IgM, develop new enzyme-linked immunosorbent assay (ELISA) using horseradish peroxidase-labeled LD5 (HRP-LD5) as conjugated enzyme complex. The...
MicroRNAs (miRNAs) and small interfering RNAs (siRNAs) are loaded into Argonaute (AGO) proteins, forming RNA-induced silencing complexes (RISCs). The assembly process establishes the seed, central, 3' supplementary, tail regions across guide, enabling RISC to recognize target for silencing. This guide segmentation is caused by anchoring end at AGO PAZ domain, but minimum length required conformation remains be studied because current miRNA size defined Dicer processing ambiguous. Using a →...
RNA thermosensors (RNATs), found in the 5′ untranslated region (UTR) of some bacterial messenger RNAs (mRNAs), control translation downstream gene a temperature-dependent manner. In Listeria monocytogenes, expression key transcription factor, PrfA, is mediated by an RNAT its UTR. PrfA functions as master regulator virulence L. controlling many factors. The temperature-regulated element serves signal successful host invasion for bacteria. Structurally, prfA bears little resemblance to known...
HIV-1 Tat is an important regulatory protein involved in AIDS pathogenesis. However, the immunoprofiles of anti-Tat responses remain unclear. We analysed antibody and neutralizing activities. Out 326 HIV-1-seropositive individuals, 12.9% were positive for antibodies. found six different immunological profiles responses: full-potential response, combined N-specific C-specific full-length Tat-specific response Tat-related response. These represent two types major complete alternative C-prone A...
MicroRNAs (miRNAs) and small interfering RNAs (siRNAs) are loaded into Argonaute (AGO) proteins, forming RNA-induced silencing complexes (RISCs). The assembly process establishes the seed, central, 3' supplementary, tail regions across guide, enabling RISC to recognize cleave target RNAs. This guide segmentation is caused by anchoring end at AGO PAZ domain, but minimum length required for conformation remains be studied because there was no method which do so. Using a 3'→5' exonuclease...
The 70‐kilodalton heat shock protein (Hsp70) interacts with tetratricopeptide repeat (TPR) domains of CHIP (C‐terminus Hsp70 Interacting Protein) and HOP (Hsp Organizing using a two‐carboxylate clamp binding mechanism. Differential affinity for the TPR are achieved through interactions six residues preceding carboxy‐terminal Asp 641 Hsp70. In particular, phosphorylation Thr 636 produces dramatic swing in affinities that shift preferential formation CHIP/Hsp70 complexes to HOP/Hsp70...
Cellular chaperones and co-chaperones maintain protein quality control (PQC) are vital to cellular stress responses. The TPR-containing CHIP (C-terminus of Hsp70 Interacting Protein, STUB1) HOP (Hsp70 Organizing STIP1) implicated in counter-regulatory mechanisms chaperone-bound client proteins by promoting degradation or folding environments, respectively. To identify influenced expression, we performed gene expression arrays analyses from mouse liver. We discovered that mice lacking the...
The C-terminus of the 70-kilodalton heat shock protein interacts with TPR domains within ubiquitin ligase CHIP (C-terminus Hsp70 interacting protein) and Hop (Hsp70-Hsp90 organizing protein). Interactions allow for formation a productive encounter complex that facilitates ubiquitination Hsp70-bound substrates, thereby targeting those proteins proteasomal degradation. In contrast, interaction coordinates active refolding in concert Hop-recruited Hsp90. Phosphorylation causes switch from...
The ubiquitin ligase CHIP plays an important role in cytosolic protein quality control by ubiquitinating proteins chaperoned Hsp70/Hsc70 and Hsp90 targeting them for degradation. We present a 2.91 Å resolution structure of the TPR domain complex with α-helical “lid” subdomain unstructured “tail” Hsc70. Surprisingly, CHIP-TPR interacts determinants within both Hsc70-lid C-terminal GPTIEEVD motif tail, exhibiting novel mode chaperone-TPR interaction. demonstrate that interaction between is...
The ubiquitin ligase CHIP catalyzes covalent attachment of to unfolded proteins chaperoned by the heat shock Hsp70/Hsc70 and Hsp90. interacts with Hsp90 binding a C-terminal IEEVD motif found in tetratricopeptide repeat (TPR) domain CHIP. Although recruitment via interaction CHIP-TPR is well established, alterations structure dynamics upon are not understood. In particular, absence for free form presents significant limitation studies seeking rationally design inhibitors that may disrupt...