Biology subjects

Dai, M.

Publications and source records attributed to Dai, M..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Development of a monoclonal antibody against duck IFN-γ protein and the application for Intracellular Cytokine Staining

ABSTRACTInterferon-{gamma} (IFN-{gamma}), a member of the type II IFN family, is a crucial cytokine in the immune system and serves as an important indicator of immune response. Intracellular Cytokine Staining (ICS) is a technique used to analyze the production of cytokines within individual cells, and it has a wide range of applications in the fields of immunological monitoring, vaccine trials, and the study of infectious diseases. This study aimed to prepare monoclonal antibodies against duck IFN-{gamma} protein and to establish an ICS protocol for detecting the duck IFN-{gamma} protein. The duIFN-{gamma}-His or duIFN-{gamma}-Fc gene was cloned into the pEE12.4 expression vector and expressed as a recombinant protein of size 20.2 KDa or 54.9 KDa in 293F cells. The purified recombinant proteins were inoculated into BALB/c mice to generate splenic lymphocytes capable of secreting anti-duIFN-{gamma} antibodies, and hybridoma cells were obtained after fusion with SP2/0 cells. A new hybridoma cell line named 24H4, which stably secreted IgG3 {kappa} subtype antibody against duck IFN-{gamma}. This monoclonal antibody (mAb) was identified by Western Blot to recognize duck IFN-{gamma} antibodies, and the indirect ELISA results showed that its ability to recognize IFN-{gamma} protein reached 0.001 g/ml. The established ICS method was used to stain PBMCs after ConA stimulation, and duck IFN-{gamma} protein was successfully detected by flow cytometry, indicating that the ICS method was successfully established. This study we use the monoclonal antibody, 24H4, provides a crucial tool for subsequent research on duck cellular immune responses.

immunology↗

bioRxiv2024

Integrative analysis of transcriptome and metabolism reveals functional roles of redox homeostasis in low light and salt combined stress in Leymus chinensis

Soil salinity (Salt) is one of the major limiting factors of Leymus chinensis (named sheepgrass) performance and alters their primary metabolic process and gene expression. Salt stress could accelerate inhibitive effects concomitant with low light (LL-Salt). However, little is known about physiological and molecular mechanisms under such LL-Salt in sheepgrass. This study aims to uncover the key reprogrammed metabolic pathways induced by LL-Salt through an integrated analysis of transcriptome and metabolism. Plant seedlings were exposed to six combinations of light intensity (moderate light, ML, and LL) and NaCl concentrations (0, 50, and 200mM) for 20 days. Results suggest that the growth of sheepgrass seedlings was dramatically inhibited with severe lodging phenotype, especially when exposed to LL-Salt combined conditions. Activities of an antioxidant enzyme, catalase, were significantly increased in LL but significantly decreased in salt stress, leading to a reverse pattern for H2O2 in LL and salt stress. Transcriptome analysis reveals 4921 downregulated differentially expressed genes (DEGs) with carbon metabolism pathways were significantly enriched compared to light response without salt (ML_0 vs LL_0). There are 194 overlapped downregulated DEGs induced by two salt treatments (ML_50 vs ML_0 and ML_200 vs ML_0), where the carbon metabolism pathway was also significantly enriched. In terms of interactive effects of LL-Salt treatments, we found that there are 16 overlapped DEGs, including a phytochrome-interacting transcription factor 4 (PIF4) with upregulation in LL treatment while downregulation in salt treatment, which was validated by qPCR. Metabolism analysis confirmed that in carbon metabolism, the contents of seven differentially abundant metabolites (DAMs), including sucrose, were all downregulated in both LL and salt treatment. In contrast, serine and glycolate in the photorespiration pathway were downregulated in LL while upregulated in salt treatment. A photorespiration regulatory gene, glycolate oxidase expression, was confirmed by qPCR. Collectively, we found that serval antioxidant redox pathways, including photorespiration, GSG/GSSH redox, and ABA signaling, participated in response to LL and salt combined events and highlighted the roles of cellular redox homeostasis in LL-Salt response in sheepgrass.

plant biology↗

bioRxiv2024

DRED: A Comprehensive Database of Genes Related to Repeat Expansion Diseases

Expansion of tandem repeats in genes often causes severe neuromuscular diseases, such as fragile X syndrome, huntingtons disease, and spinocerebellar ataxia. However, information on genes associated with repeat expansion diseases is scattered throughout the literature, systematic prediction of potential genes that may cause diseases via repeat expansion is also lacking. Here, we develop DRED, a Database of genes related to Repeat Expansion Diseases, as a manually-curated database that covers all known 61 genes related to repeat expansion diseases reported in PubMed and OMIM, along with detailed repeat information for each gene. DRED also includes 516 genes with the potential to cause diseases via repeat expansion, which were predicted basing on their repeat composition, genetic variations, genomic features, and disease associations. Various types of information on repeat expansion diseases and their corresponding genes/repeats are presented in DRED, together with links to external resources, such as NCBI and ClinVar. DRED provides user-friendly interfaces with comprehensive functions, and can serve as a central data resource for basic research and repeat expansion disease-related medical diagnosis. DRED is freely accessible at http://omicslab.genetics.ac.cn/dred, and is frequently updated to include newly reported genes related to repeat expansion diseases.

bioinformatics↗

bioRxiv2024

Discovery of novel quinoline papain-like protease inhibitors for COVID-19 through topology constrained molecular generative model

The rapid emergence of drug-resistant SARS-CoV-2 variants poses a persistent challenge to current antiviral strategies. Mutations in key viral targets, including RNA-dependent RNA polymerase (RdRp), main protease (3CLpro), and papain-like protease (PLpro), have been shown to markedly reduce the efficacy of approved therapeutics, highlighting the urgent need for next-generation antivirals capable of overcoming resistance. Here, we report the discovery of a novel class of PLpro inhibitors through an AIDD strategy based on a topology-constrained molecular generative model (Tree-Invent) integrated with structure-guided optimization. Scaffold hopping from a previously reported lead enabled the identification of a quinoline-based chemical series with substantially improved metabolic stability and antiviral potency. Structure-guided optimization yielded compound GZNL-2016, which exhibited potent enzymatic inhibition of PLpro (IC50 = 10.5 nM), robust antiviral activity against multiple SARS-CoV-2 variants, including Omicron BA.5 and XBB.1, and favorable pharmacokinetic properties following oral administration. Notably, GZNL-2016 retained substantial inhibitory activity against the clinically relevant drug-resistant mutant PLpro E167K (IC50 = 480.2 nM; Ki = 439.3 nM), in contrast to previously reported inhibitors that exhibit markedly reduced potency. In a SARS-CoV-2 infection mouse model, oral administration of GZNL-2016 significantly reduced pulmonary viral titers, demonstrating in vivo antiviral efficacy. Collectively, this study establishes an AI-enabled strategy for rapid antiviral discovery and identifies GZNL-2016 as a promising lead compound to address the threat of coronavirus infections caused by drug-resistant mutant SARS-CoV-2 variants. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC="FIGDIR/small/611841v3_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@ecbd3eorg.highwire.dtl.DTLVardef@7c663corg.highwire.dtl.DTLVardef@11c0e37org.highwire.dtl.DTLVardef@e950f0_HPS_FORMAT_FIGEXP M_FIG C_FIG We leveraged an AI generative model to discover a novel PLpro inhibitor with excellent liver stability, low CYP, hERG inhibition and reasonable oral PK properties. At the same time, the compound 16 exhibits high efficacy for the resistance mutation E167K, which resulted in severe resistance to the previously reported inhibitor Jun12682 and PF-07957472.

microbiology↗

bioRxiv2024

An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes

In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools to access and manipulate specific neuronal subtypes are still limited. Here, we performed systematic analysis of single cell genomic data to identify enhancer candidates for each of the telencephalic interneuron subtypes. We established a set of enhancer-AAV tools that are highly specific for distinct cortical interneuron populations and striatal cholinergic interneurons. These enhancers, when used in the context of different effectors, can target (fluorescent proteins), observe activity (GCaMP) and manipulate (opto-genetics) specific neuronal subtypes. We also validated our enhancer-AAV tools across species. Thus, we provide the field with a powerful set of tools to study neural circuits and functions and to develop precise and targeted therapy.

neuroscience↗

bioRxiv2024

Pyramidal neurons proportionately alter the identity and survival of specific cortical interneuron subtypes

The mammalian cerebral cortex comprises a complex neuronal network that maintains a precise balance between excitatory pyramidal neurons and inhibitory interneurons. Accumulating evidence indicates that specific interneuron subtypes form stereotyped microcircuits with distinct pyramidal neuron classes. Here we show that pyramidal neurons play an active role in this process by promoting the survival and terminal differentiation of their associated interneuron subtypes. In wild-type cortex, interneuron subtype abundance mirrors the prevalence of their pyramidal neuron partners. In Fezf2 mutants, which lack layer 5b pyramidal neurons and are expanded in layer 6 intratelencephalic neurons, corresponding subtype-specific shifts occur through two distinct mechanisms: somatostatin interneurons adjust their programmed cell death, whereas parvalbumin interneurons switch their subtype identity. Silencing neuronal activity or blocking vesicular release in L5b pyramidal neurons revealed that their communication with interneurons does not require voltage-gated synaptic activity and engages both tetanus toxin-sensitive and -insensitive pathways. Moreover, a targeted bioinformatic screen for ligand-receptor pairs displaying subtype-specific expression and reduced expression of pyramidal neuron-derived ligand in Fezf2 mutants identified candidate secreted factors and adhesion molecules. These findings reveal distinct, pyramidal neuron-driven mechanisms for sculpting interneuron diversity and integrating them into local cortical circuits.

neuroscience↗

bioRxiv2024

BRAT1 - a new therapeutic target for glioblastoma

Glioblastoma (GBM), the most malignant primary brain tumor in adults, has poor prognosis irrespective of therapeutic advances due to its radio-resistance and infiltrative growth into brain tissue. The present study assessed functions and putative druggability of protein breast cancer type 1 susceptibility protein (BRCA1)-associated Ataxia telangiectasia mutated (ATM)-activator 1 (BRAT1) as a crucial factor driving key aspects of GBM, including enhanced DNA damage response and tumor migration. By a stable depletion of BRAT1 in GBM and glioma stem-like (GSC) cell lines, we observed a delay in DNA double-strand break repair and increased sensitivity to radiation treatment, corroborated by in vitro and in vivo studies demonstrating impaired tumor growth and invasion. Proteomic analyses further emphasize the role of BRAT1s cell migration and invasion capacity, with a notable proportion of downregulated proteins associated with these processes. In line with the genetic manipulation, we found that treatment with the BRAT1 inhibitor Curcusone D (CurD) significantly reduced GSC migration and invasion in an ex vivo slice culture model, particularly when combined with irradiation, resulting a synergistic inhibition of tumor growth and infiltration. Our results reveal that BRAT1 contributes to GBM growth and invasion and suggest that therapeutic inhibition of BRAT1 with CurD or similar compounds might constitute a novel approach for anti-GBM directed treatments.

cancer biology↗

bioRxiv2024

Discovery of orally bioavailable SARS-CoV-2 papain-like protease inhibitor as a potential treatment for COVID-19

The RNA-dependent RNA polymerase (RdRp), 3C-like protease (3CLpro), and papain-like protease (PLpro) are pivotal components in the viral life cycle of SARS-CoV-2, presenting as promising therapeutic targets. Currently, all FDA-approved antiviral drugs against SARS-CoV-2 are RdRp or 3CLpro inhibitors. However, the mutations causing drug resistance have been observed in RdRp and 3CLpro from SARS-CoV-2, which makes it necessary to develop antivirals with novel mechanisms. Through the application of a structure-based drug design (SBDD) approach, we discovered a series of novel potent non-covalent PLpro inhibitors with remarkable in vitro potency and in vivo PK properties. The co-crystal structures of PLpro with leads revealed that the residues D164 and Q269 around the S2 site are critical for improving the inhibitors potency. The lead compound GZNL-P36 not only inhibited SARS-CoV-2 and its variants at the cellular level with EC50 ranging from 58.2 nM to 306.2 nM, but also inhibited HCoV-NL63 and HCoV-229E with EC50 of 81.6 nM and 2.66 M, respectively. Oral administration of the compound resulted in significantly improved survival and notable reductions in lung viral loads and lesions in SARS- CoV-2 infection mouse model, consistent with RNA-seq data analysis. Our results indicate that PLpro inhibitor is a promising SARS-CoV-2 therapy.

microbiology↗

bioRxiv2024

Peptide Amphiphiles Hitchhike on Endogenous Biomolecules for Enhanced Cancer Imaging and Therapy

The interactions of nanomaterials with biomolecules in vivo determine their biological fate. Here, we show that self-assembled peptide amphiphile (PA) nanostructures can dynamically interact with endogenous biomolecules and take advantage of naturally occurring processes to target a broad range of solid tumors. In circulation, self-assembled PA nanostructures disassemble and reassemble mainly with lipoproteins, which prolongs blood circulation and dramatically improves tumor accumulation and retention. Mechanistic studies suggested that PAs internalize into cancer cells by assembling with their cell membranes and independently of specific receptors. By exploiting these interactions, a PA developed in this study (namely SA-E) demonstrated specific accumulation in various xenograft, syngeneic, patient-derived xenograft, or transgenic rodent models. In addition, SA-E enabled the effective delivery of highly potent chemotherapy to different syngeneic and xenografted tumors with reduced side effects. With its simple and modular design and universal tumor accumulation mechanism, SA-E represents a promising platform for broad applications in cancer imaging and therapy.

bioengineering↗

bioRxiv2024

Generalizable Quantum Computing Pipeline for Real World Drug Discovery

Quantum computing, with its superior computational capabilities compared to classical approaches, holds the potential to revolutionize numerous scientific domains, including pharmaceuticals. However, the application of quantum computing for drug discovery has primarily been limited to proof-of-concept studies, which often fail to capture the intricacies of real-world drug development challenges. In this study, we diverge from conventional investigations by developing an advanced quantum computing pipeline tailored to address genuine drug design problems. Our approach underscores the pragmatic application of quantum computation and propels it towards practical industrial adoption. We specifically construct our versatile quantum computing pipeline to address two critical tasks in drug discovery: the precise determination of Gibbs free energy profiles for prodrug activation involving covalent bond cleavage, and the accurate simulation of covalent bond interactions. This work serves as a pioneering effort in benchmarking quantum computing against veritable scenarios encountered in drug design, especially the covalent bonding issue present in both of the case studies, thereby transitioning from theoretical models to tangible applications. Our results demonstrate the potential of a quantum computing pipeline for integration into real world drug design workflows.

bioinformatics↗

bioRxiv2023

A dipteran parasite regulates 20E synthesis and antibacterial activity of the host for development through inducing host nitric oxide production

Parasites primarily rely on the host to survive, and have evolved diverse survival strategies. In the present study, we report a specific survival strategy of a dipteran parasite Exorista sorbillans (Diptera: Tachinidae), which is a potential biological control agent for agricultural pests and a pest in sericulture. We found that the expression levels of host nitric oxide synthase (NOS) and nitric oxide (NO) production were increased after E. sorbillans infection. Reducing NOS expression and NO production with a NOS inhibitor (L-NAME) in infected hosts significantly impeded the growth of E. sorbillans larvae. Moreover, the 20-hydroxyecdysone (20E) biosynthesis of infected hosts was elevated with increasing NO production, and inhibiting NOS expression also lowered 20E biosynthesis. More importantly, induced NO synthesis was required to eliminate intracellular bacterial pathogens that presumably competed for shared host resources. Inhibiting NOS expression down-regulated the transcription of antimicrobial peptide genes and increased the number of bacteria in infected hosts. Collectively, this study revealed a new perspective on the role of NO in host-parasite interactions and a novel mechanism for parasite regulation of host to support its development. Author summaryParasites are ubiquitous on earth and diverse, and have evolved various strategies to match their own specific requirements for survival within the host. In this study, we found that Exorista sorbillans, an endoparasite of many agricultural pests and the main insect pest in sericulture, used a novel strategy to manipulate its host NO synthesis for survival within its host Bombyx mori. Specifically, NOS expression and the production of NO in the host were up-regulated by E. sorbillans infection, which benefited larval E. sorbillans development. Meanwhile, increased NO production in host activated 20E synthesis of parasitized hosts and triggered the expression of AMPs against the invasion of pathogenic bacteria to avoid nutritional competence in the host. Our study provides innovative insights into the mechanisms by which a parasite manipulates host NO production for development and may help to expand our knowledge of other parasitic systems.

pathology↗

bioRxiv2023

Mitochondrial genome evolution in the Diprionidae: Major gene rearrangement in the basal Hymenoptera

In comparison to other non-parasitic basal lineages, Apocrita have consistently demonstrated a greatly accelerated rate of gene rearrangement. A number of mechanisms or correlates have been proposed for this observation, such as oxidative stress tolerated by exposure to the host immune system might lead to a high proportion of rearranged mt-genomes. Our studies reveal that gene rearrangements involving the protein-coding gene are present in the basal Hymenoptera lineage based on enriched sampling. We speculate the processes of diversification of rearrangements in the vicinity of nad2 involved tRNAs and NCRs by producing the chronogram of Diprionids. Furthermore, we investigated the relationship between rearranged genes and their nucleotide sequences. In conclusion, we demonstrate the great potential of gene order and associated sequence features as phylogenetic markers in the study of Hymenoptera evolution, offering a new perspective on studying organisms that undergo frequent gene rearrangements.

evolutionary biology↗

bioRxiv2022

A Unified Catalog of 19,251 Non-human Reference Species Genomes Provides New Insights into the Mammalian Gut Microbiomes

The gut microbiota is essential for host health and survival. Here, using samples from animals living in the Qinghai-Tibetan Plateau, we recovered 119,568 metagenome-assembled genomes (MAGs) that were clustered into 19,251 species-level genome bins (SGBs) of which most represent novel species. We present a novel mechanism shaping mammalian gut microbiomes using ancestral founder bacteria (AFB) as a core skeleton and recurring lineage-specific gains of microbial species that are transferred frequently among multiple hosts, not strictly limited by host phylogeny. Such lineage specific gains are responsible for increasing gut microbial diversity, maintaining functional stability, and endowing specific functions for host adaptions. Our analyses did not support the existence of co-phylogeny or co-speciation events between mammal hosts and their individual gut symbionts. The results presented in this study not only reveal novel unique gut microbial species and offer insight of value for understanding the diversity, stability, functionality of the mammalian gut microbiomes, and the co-evolution with their hosts, but also emphasize that animals living in extreme environments are a promising resource for the discovery of novel biological functions.

microbiology↗

bioRxiv2022

Conserved cell-type specific signature of resilience to Alzheimer's disease nominates role for excitatory cortical neurons

Alzheimers disease (AD), the leading cause of dementia, affects millions of people worldwide. With no disease-modifying medication currently available, the human toll and economic costs are rising rapidly. Under current standards, a patient is diagnosed with AD when both cognitive decline and pathology (amyloid plaques and neurofibrillary tangles) are present. Remarkably, some individuals who have AD pathology remain cognitively normal. Uncovering factors that lead to "cognitive resilience" to AD is a promising path to create new targets for therapies. However, technical challenges discovering novel human resilience factors limit testing, validation, and nomination of novel drugs for AD. In this study, we use single-nucleus transcriptional profiles of postmortem cortex from human individuals with high AD pathology who were either cognitively normal (resilient) or cognitively impaired (susceptible) at time of death, as well as mouse strains that parallel these differences in cognition with high amyloid load. Our cross-species discovery approach highlights a novel role for excitatory layer 4/5 cortical neurons in promoting cognitive resilience to AD, and nominates several resilience genes that include ATP1A1, GRIA3, KCNMA1, and STXBP1. This putative cell type has been implicated in resilience in previous studies on bulk RNA-seq tissue, but our single-nucleus and cross-species approach identifies particular resilience-associated gene signatures in these cells. These novel resilience candidate genes were tested for replication in orthogonal data sets and confirmed to be correlated with cognitive resilience. Based on these gene signatures, we identified several potential mechanisms of resilience, including regulation of synaptic plasticity, axonal and dendritic development, and neurite vesicle transport along microtubules that are potentially targetable by available therapeutics. Because our discovery of resilience-associated genes in layer 4/5 cortical neurons originates from an integrated human and mouse transcriptomic space from susceptible and resilient individuals, we are positioned to test causality and perform mechanistic, validation, and pre-clinical studies in our human-relevant AD-BXD mouse panel.

neuroscience↗

bioRxiv2022

Hypothalamic gene network dysfunction is associated with cognitive decline and body weight loss in Alzheimer's disease mice

Recent studies, both clinical and experimental, indicate that many neurodegenerative disorders including Alzheimers disease (AD) often display coexisting metabolic dysfunctions, which may exacerbate neurological symptoms. The hypothalamus is a brain region highly involved in maintaining metabolic and other homeostatic processes and is known to be involved in the etiology of AD, although the role of hypothalamic dysfunction in the onset, progression, and severity of AD is poorly understood. In this study, we demonstrate that our new model of genetic diversity in AD, the AD-BXDs, exhibits non-cognitive symptoms consistent with hypothalamic dysfunction and examined hypothalamic bulk RNA sequencing data in the AD-BXD panel to investigate how the AD transgene impacts gene expression profiles in the hypothalamus. Mostly notably, we identified strong neuroinflammatory signatures from the hypothalamus in the AD-BXDs as early as six months of age. A functionally unknown WGCNA module showed correlation to female body weight and contextual fear acquisition. Eigengene expression of microglial/macrophagic modules and their hub gene expressions were correlated to cognitive phenotypes. From these analyses, we nominated Plek and Laptm5 as new targets to attenuate neuroinflammation in AD.

neuroscience↗

bioRxiv2022

LIPA-driven hydrolysis of cholesteryl arachidonate promotes cancer metastasis via NF-κB

Cholesteryl ester (CE) is an established marker in many types of aggressive cancers. Yet, the function of CE homeostasis during cancer progression is largely unknown. Here, enabled by Raman spectromicroscopy, pan-cancer bioinformatic analysis, and biocompatible Raman probe of cholesterol, LIPA was identified as the key regulator of CE hydrolysis in cancer cells. LIPA inhibition induced aberrant accumulation of CE-rich lipid droplet at single cell level. LIPA-driven CE hydrolysis was directly visualized by stimulated Raman scattering imaging of alkyne-tagged cholesterol. Cholesteryl arachidonate was identified as a dominant substrate that is rapidly hydrolyzed by LIPA. Inhibition of LIPA effectively suppressed cancer metastasis both in vitro and in vivo. Mechanistically, LIPA inhibition suppresses NF-{kappa}B signaling, while the NF-{kappa}B members positively regulate the expression level of LIPA, indicating regulation of CE homeostasis by a LIPA-CE-NF{kappa}B feedback loop. Collectively, our findings reveal that LIPA drives CE hydrolysis during cancer progression and is an important metabolic target for cancer therapy.

cancer biology↗

bioRxiv2021

Accurate and fast cell marker gene identification with COSG

Accurate cell classification is the groundwork for downstream analysis of single-cell sequencing data, yet how to identify marker genes to distinguish different cell types still remains as a big challenge. We developed COSG as a cosine similarity-based method for more accurate and scalable marker gene identification. COSG is applicable to single-cell RNA sequencing data, single-cell ATAC sequencing data and spatially resolved transcriptome data. COSG is fast and scalable for ultra-large datasets of million-scale cells. Application on both simulated and real experimental datasets demonstrates the superior performance of COSG in terms of both accuracy and efficiency as compared with other available methods. Marker genes or genomic regions identified by COSG are more indicative and with greater cell-type specificity.

bioinformatics↗

bioRxiv2021

Structural insights into the activation of human calcium-sensing receptor

Human calcium-sensing receptor (CaSR) is a G-protein-coupled receptor that maintains Ca2+ homeostasis in serum. Here, we present the cryo-electron microscopy structures of the CaSR in the inactive and active states. Complemented with previously reported crystal structures of CaSR extracellular domains, it suggests that there are three distinct conformations: inactive, intermediate and active state during the activation. We used a negative allosteric nanobody to stabilize the CaSR in the fully inactive state and found a new binding site for Ca2+ ion that acts as a composite agonist with L-amino acid to stabilize the closure of active Venus flytraps. Our data shows that the agonist binding leads to the compaction of the dimer, the proximity of the cysteine-rich domains, the large-scale transitions of 7-transmembrane domains, and the inter-and intrasubunit conformational changes of 7-transmembrane domains to accommodate the downstream transducers. Our results reveal the structural basis for activation mechanisms of the CaSR.

biophysics↗