Immunoglobulin G (IgG) is traditionally recognized as a plasma protein that neutralizes antigens for immune defense. However, our research demonstrates that IgG predominantly accumulates in adipose tissue during obesity development, triggering insulin resistance and macrophage infiltration. This accumulation is governed by neonatal Fc receptor (FcRn)-dependent recycling, orchestrated in adipose progenitor cells and macrophages during the early and late stages of diet-induced obesity (DIO), respectively.
View Article and Find Full Text PDFFerroptosis, a regulated form of cell death characterized by excessive iron-dependent lipid peroxidation, can be readily induced in cultured cells by chemicals such as erastin and RSL3. Protein disulfide isomerase (PDI) has been identified as an upstream mediator of chemically induced ferroptosis and also a target for ferroptosis protection. In this study, we discovered that raloxifene (RAL), a selective estrogen receptor modulator known for its neuroprotective actions in humans, can effectively inhibit PDI function and provide robust protection against chemically induced ferroptosis in cultured HT22 neuronal cells.
View Article and Find Full Text PDFProtein-Protein binding affinity reflects the binding strength between the binding partners. The prediction of protein-protein binding affinity is important for elucidating protein functions and also for designing protein-based therapeutics. The geometric characteristics such as area (both interface and surface areas) in the structure of a protein-protein complex play an important role in determining protein-protein interactions and their binding affinity.
View Article and Find Full Text PDFSpecific antibodies can bind to protein antigens with high affinity and specificity, and this property makes them one of the best protein-based therapeutics. Accurate prediction of antibody‒protein antigen binding affinity is crucial for designing effective antibodies. The current predictive methods for protein‒protein binding affinity usually fail to predict the binding affinity of an antibody‒protein antigen complex with a comparable level of accuracy.
View Article and Find Full Text PDFCurr Pharm Biotechnol
March 2023
The market demand for recombinant therapeutic proteins (RTPs) has promoted the development of various protein expression host and bioprocessing technologies. Since mammalian cells have the unique advantage of being able to direct the correct folding of proteins and provide post-translational processing such as complex glycosylation, the RTPs produced by them currently account for approximately 80% of the approved marketed RTPs. Among them, Chinese hamster ovary (CHO) cells are currently the preferred host cells for the production of RTPs.
View Article and Find Full Text PDFProtein-protein interaction plays an important role in all biological systems. The binding affinity between two protein binding partners reflects the strength of their association, which is crucial to the elucidation of the biological functions of these proteins and also to the design of protein-based therapeutic agents. In recent years, many studies have been conducted in an effort to improve the ability to predict the binding affinity of a protein-protein complex.
View Article and Find Full Text PDFHuman microsomal triglyceride transfer protein (hMTP) plays an essential role in the assembly of apoB-containing lipoproteins, and has become an important drug target for the treatment of several disease states, such as abetalipoproteinemia, fat malabsorption and familial hypercholesterolemia. hMTP is a heterodimer composed of a larger hMTPα subunit and a smaller hMTPβ subunit (namely, protein disulfide isomerase, hPDI). hPDI can interact with 17β-estradiol (E), an endogenous female sex hormone.
View Article and Find Full Text PDFActa Biochim Biophys Sin (Shanghai)
July 2021
Insulin receptor plays an important role in the regulation of energy metabolism. Dysfunction of insulin receptor (IR) can lead to many disease states, such as diabetes mellitus. Deciphering the complex dynamic structures of human IR and its mechanism of activation would greatly aid in understanding IR-mediated signaling pathways and also in designing new drugs (including nonpeptidal insulin analogs) to treat diabetes mellitus.
View Article and Find Full Text PDFThe transporter MsbA is a kind of multidrug resistance ATP-binding cassette transporter that can transport lipid A, lipopolysaccharides, and some amphipathic drugs from the cytoplasmic to the periplasmic side of the inner membrane. In this work, we explored the allosteric pathway of MsbA from the inward- to outward-facing states during the substrate transport process with the adaptive anisotropic network model. The results suggest that the allosteric transitions proceed in a coupled way.
View Article and Find Full Text PDFThe maltose transporter from Escherichia coli is one of the ATP-binding cassette (ABC) transporters that utilize the energy from ATP hydrolysis to translocate substrates across cellular membranes. Until 2011, three crystal structures have been determined for maltose transporter at different states in the process of transportation. Here, based on these crystal structures, the allosteric pathway from the resting state (inward-facing) to the catalytic intermediate state (outward-facing) is studied by applying an adaptive anisotropic network model.
View Article and Find Full Text PDFUnderstanding the key factors that influence the preferences of residue-nucleotide interactions in specific protein-RNA interactions has remained a research focus. We propose an effective approach to derive residue-nucleotide propensity potentials through considering both the types of residues and nucleotides, and secondary structure information of proteins and RNAs from the currently largest nonredundant and nonribosomal protein-RNA interaction database. To test the validity of the potentials, we used them to select near-native structures from protein-RNA docking poses.
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