51,705 results match your criteria binding c-terminal

Peculiarities of the Presentation of the Encephalitogenic MBP Peptide by HLA-DR Complexes Providing Protection and Predisposition to Multiple Sclerosis.

Acta Naturae 2021 Jan-Mar;13(1):127-133

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences, Moscow, 117997 Russia.

Predisposition to multiple sclerosis (MS), a chronic autoimmune disease of the central nervous system, is due to various factors. The genetic component is considered one of the most important factors. HLA class II genes contribute the most to the development of MS. Read More

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Structural basis of chitin utilization by a GH20 β-N-acetylglucosaminidase from Vibrio campbellii strain ATCC BAA-1116.

Acta Crystallogr D Struct Biol 2021 May 27;77(Pt 5):674-689. Epub 2021 Apr 27.

Biochemistry-Electrochemistry Research Unit, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.

Vibrio species play a crucial role in maintaining the carbon and nitrogen balance between the oceans and the land through their ability to employ chitin as a sole source of energy. This study describes the structural basis for the action of the GH20 β-N-acetylglucosaminidase (VhGlcNAcase) in chitin metabolism by Vibrio campbellii (formerly V. harveyi) strain ATCC BAA-1116. Read More

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Attenuation of inhibitory PAS domain protein-induced cell death by synthetic peptides derived from Mcl-1 transmenbrane domain.

Cell Death Discov 2021 May 4;7(1):92. Epub 2021 May 4.

Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Aoba-ku Sendai, 980-8578, Japan.

Expression of Inhibitory PAS domain protein (IPAS) induces apoptosis by inhibiting the anti-apoptotic activity of mitochondrial pro-survival proteins including Bcl-x and Mcl-1 through direct binding. Analysis to examine the IPAS-binding region in Bcl-x demonstrated that the C-terminal transmembrane (TM) domain is indispensable for the specific binding. A chimeric protein composed of the TM domain of Mcl-1 fused to the C-terminus of Citrine also exhibited a binding affinity to IPAS, and markedly attenuated apoptosis caused by the overexpression of Cerulean-IPAS in SH-SY5Y cells. Read More

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Structural analysis of the PTEN:P-Rex2 signaling complex reveals how cancer-associated mutations coordinate to hyperactivate Rac1.

Sci Signal 2021 May 4;14(681). Epub 2021 May 4.

Biomedicine Discovery Institute, Monash University, Clayton, 3800 Victoria, Australia.

The dual-specificity phosphatase PTEN functions as a tumor suppressor by hydrolyzing PI(3,4,5)P to PI(4,5)P to inhibit PI3K-AKT signaling and cellular proliferation. P-Rex2 is a guanine nucleotide exchange factor for Rho GTPases and can be activated by Gβγ subunits downstream of G protein-coupled receptor signaling and by PI(3,4,5)P downstream of receptor tyrosine kinases. The PTEN:P-Rex2 complex is a commonly mutated signaling node in metastatic cancer. Read More

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Streptococcus pneumoniae Binds to Host Lactate Dehydrogenase via PspA and PspC To Enhance Virulence.

mBio 2021 05 4;12(3). Epub 2021 May 4.

Department of Microbiology, The University of Alabama at Birmingham, Birmingham, Alabama, USA

Pneumococcal surface protein A (PspA) and pneumococcal surface protein C (PspC, also called CbpA) are major virulence factors of (). These surface-exposed choline-binding proteins (CBPs) function independently to inhibit opsonization, neutralize antimicrobial factors, or serve as adhesins. PspA and PspC both carry a proline-rich domain (PRD) whose role, other than serving as a flexible connector between the N-terminal and C-terminal domains, was up to this point unknown. Read More

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Engineering the Modular Receptor-Binding Proteins of Phages Switches Their Capsule Serotype Specificity.

mBio 2021 05 4;12(3). Epub 2021 May 4.

Department of Biotechnology, Ghent University, Ghent, Belgium

The high specificity of bacteriophages is driven by their receptor-binding proteins (RBPs). Many bacteriophages target the capsular exopolysaccharide as the receptor and encode RBPs with depolymerase activity. The modular structure of these RBPs with an N-terminal structural module to attach the RBP to the phage tail, and a C-terminal specificity module for exopolysaccharide degradation, supports horizontal transfer as a major evolutionary driver for phage RBPs. Read More

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Experimental evolution in morbidostat reveals converging genomic trajectories on the path to triclosan resistance.

Microb Genom 2021 May;7(5)

Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.

Understanding the dynamics and mechanisms of acquired drug resistance across major classes of antibiotics and bacterial pathogens is of critical importance for the optimization of current anti-infective therapies and the development of novel ones. To systematically address this challenge, we developed a workflow combining experimental evolution in a morbidostat continuous culturing device with deep genomic sequencing of population samples collected in time series. This approach was applied to the experimental evolution of six populations of BW25113 towards acquiring resistance to triclosan (TCS), an antibacterial agent in various consumer products. Read More

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The translation initiation factor EIF4E5 from Leishmania: crystal structure and interacting partners.

RNA Biol 2021 May 4:1-17. Epub 2021 May 4.

Departamento de Microbiologia, Instituto Aggeu Magalhães, FIOCRUZ-PE, Av. Moraes Rego s/n, Recife-PE, Brazil.

The mRNA cap-binding protein, eIF4E, mediates the recognition of the mRNA 5' end and, as part of the heterotrimeric eIF4F complex, facilitates the recruitment of the ribosomal subunits to initiate eukaryotic translation. Various regulatory events involving eIF4E and a second eIF4F subunit, eIF4G, are required for proper control of translation initiation. In pathogenic trypanosomatids, six eIF4Es and five eIF4Gs have been described, several forming different eIF4F-like complexes with yet unresolved roles. Read More

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Clinical and molecular genetic analysis of a Chinese family with hereditary elliptocytosis caused by a novel mutation in the EPB41 gene.

J Clin Lab Anal 2021 May 4:e23781. Epub 2021 May 4.

Department of Laboratory Medicine, the First Affiliated Hospital of Shantou University Medical College, Shantou, P.R. China.

Background: Hereditary elliptocytosis (HE) is a heterogeneous red blood cell membrane disorder characterized by the presence of elliptocytes on a peripheral blood smear. Clinical manifestations of HE vary widely from asymptomatic carriers to patients with severe transfusion-dependent anemia. Most patients are asymptomatic or have mild anemia, which hinders diagnosis. Read More

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Cannabinoid Receptor 1 associates to different molecular complexes during GABAergic neuron maturation.

J Neurochem 2021 May 3. Epub 2021 May 3.

Laboratory of Neuroinflammation, Hospital Nacional de Paraplejicos (SESCAM), Toledo, Spain.

CB cannabinoid receptor is widely expressed in the central nervous system of animals from late prenatal development to adulthood. Appropriate activation and signaling of CB cannabinoid receptors in cortical interneurons are crucial during perinatal/postnatal ages and adolescence, when long-lasting changes in brain activity may elicit subsequent appearance of disorders in the adult brain. Here we used an optimized immunoprecipitation protocol based on specific antibodies followed by shot-gun proteomics to find CB interacting partners in postnatal rat GABAergic cortical neurons in vitro at two different stages of maturation. Read More

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Molecular analysis of the erythroid phenotype of a patient with BCL11A haploinsufficiency.

Blood Adv 2021 May;5(9):2339-2349

Academic Center for Hemoglobinopathies and Rare Anemias.

The BCL11A gene encodes a transcriptional repressor with essential functions in multiple tissues during human development. Haploinsufficiency for BCL11A causes Dias-Logan syndrome (OMIM 617101), an intellectual developmental disorder with hereditary persistence of fetal hemoglobin (HPFH). Due to the severe phenotype, disease-causing variants in BCL11A occur de novo. Read More

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15N CPMG Relaxation Dispersion for the Investigation of Protein Conformational Dynamics on the µs-ms Timescale.

J Vis Exp 2021 Apr 19(170). Epub 2021 Apr 19.

Department of Chemistry, Iowa State University; Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University;

Protein conformational dynamics play fundamental roles in regulation of enzymatic catalysis, ligand binding, allostery, and signaling, which are important biological processes. Understanding how the balance between structure and dynamics governs biological function is a new frontier in modern structural biology and has ignited several technical and methodological developments. Among these, CPMG relaxation dispersion solution NMR methods provide unique, atomic-resolution information on the structure, kinetics, and thermodynamics of protein conformational equilibria occurring on the µs-ms timescale. Read More

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Targeting novel human transient receptor potential ankyrin 1 splice variation with splice-switching antisense oligonucleotides.

Pain 2021 Jan 26. Epub 2021 Jan 26.

aDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore bElectrophysiology Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, Singapore cHealthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Centre for Life Sciences, Singapore dCardiovascular Diseases Program, National University of Singapore, Singapore eInstitute of Molecular and Cell Biology, A*STAR Research Entities, Singapore fNational Neuroscience Institute, Jalan Tan Tock Seng, Singapore gNUS Graduate School for Integrative Sciences and Engineering, Singapore hLSI Neurobiology Programme, National University of Singapore, Singapore.

Activation of transient receptor potential ankyrin 1 (TRPA1) channels by both environmental irritants and endogenous inflammatory mediators leads to excitation of the nerve endings, resulting in acute sensation of pain, itch, or chronic neurogenic inflammation. As such, TRPA1 channels are actively pursued as therapeutic targets for various pathological nociception and pain disorders. We uncovered that exon 27 of human TRPA1 (hTRPA1) could be alternatively spliced into hTRPA1_27A and hTRPA1_27B splice variants. Read More

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January 2021

Membrane Interactions of the Peroxisomal Proteins PEX5 and PEX14.

Front Cell Dev Biol 2021 16;9:651449. Epub 2021 Apr 16.

Bavarian NMR Center, Department Chemie, Technische Universität München, Munich, Germany.

Human PEX5 and PEX14 are essential components of the peroxisomal translocon, which mediates import of cargo enzymes into peroxisomes. PEX5 is a soluble receptor for cargo enzymes comprised of an N-terminal intrinsically disordered domain (NTD) and a C-terminal tetratricopeptide (TPR) domain, which recognizes peroxisomal targeting signal 1 (PTS1) peptide motif in cargo proteins. The PEX5 NTD harbors multiple WF peptide motifs (WxxxF/Y or related motifs) that are recognized by a small globular domain in the NTD of the membrane-associated protein PEX14. Read More

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Genome wide identification, phylogeny, and synteny analysis of family in common carp ().

Biotechnol Rep (Amst) 2021 Jun 16;30:e00607. Epub 2021 Mar 16.

Division of Fish Genetics and Biotechnology, Fauclty of Fisheries Rangil, Ganderbal, SKUAST-Kashmir, India.

Common carp () is a commercial fish species valuable for nutritious components and plays a vital role in human healthy nutrition. The SOX (SRY-related genes systematically characterized by a high-mobility group HMG-box) encoded important gene regulatory proteins, a family of transcription factors found in a broad range of animal taxa and extensively known for its contribution in multiple developmental processes including contribution in sex determination across phyla. In our current study, we initially accomplished a genome-wide analysis to report the SOX gene family in common carp fish based on available genomic sequences of zebrafish retrieved from gene repository databases, we focused on the global identification of the Sox gene family in Common carp among wide range of vertebrates and teleosts based on bioinformatics tools and techniques and explore the evolutionary relationships. Read More

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Modelling studies reveal the importance of the C-terminal inter motif loop of NSP1 as a promising target site for drug discovery and screening of potential phytochemicals to combat SARS-CoV-2.

J Mol Graph Model 2021 Apr 19;106:107920. Epub 2021 Apr 19.

Biomolecular Crystallography Lab, Department of Bioinformatics, School of Chemical & Biotechnology, SASTRA Deemed University, Thanjavur, 613401, India. Electronic address:

COVID-19 pandemic causative SARS-CoV-2 coronavirus is still rapid in progression and transmission even after a year. Understanding the viral transmission and impeding the replication process within human cells are considered as the vital point to control and overcome COVID-19 infection. Non-structural Protein 1, one among the proteins initially produced upon viral entry into human cells, instantly binds with the human ribosome and inhibit the host translation process by preventing the mRNA attachment. Read More

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The differential solvent exposure of N-terminal residues provides 'fingerprints' of alpha-synuclein fibrillar polymorphs.

J Biol Chem 2021 Apr 29:100737. Epub 2021 Apr 29.

Laboratory of Neurodegenerative Diseases, Institut Francois Jacob (MIRCen), CNRS, CEA, University Paris-Saclay, 92265 Fontenay-Aux-Roses cedex, France.

Synucleinopathies are neurodegenerative diseases characterized by the presence of intracellular deposits containing the protein alpha-synuclein (aSYN) within patients' brains. It has been shown that aSYN can form structurally distinct fibrillar assemblies, also termed polymorphs. We previously showed that distinct aSYN polymorphs assembled in vitro, named fibrils, ribbons and fibrils 91, differentially bind to and seed the aggregation of endogenous aSYN in neuronal cells, which suggests that distinct synucleinopathies may arise from aSYN polymorphs. Read More

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Discovery of a covalent inhibitor of heat shock protein 90 with antitumor activity that blocks the co-chaperone binding via C-terminal modification.

Cell Chem Biol 2021 Apr 26. Epub 2021 Apr 26.

State Key Laboratory of Natural Medicines, and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Heat shock protein (Hsp90), a critical molecular chaperone that regulates the maturation of a large number of oncogenic client proteins, plays an essential role in the growth of neoplastic cells. Herein, DDO-6600 is identified to covalent modification of Cys598 on Hsp90 from in silico study and is verified by a series of biological assays. We demonstrated that DDO-6600 covalently bound to Cys598 on the Hsp90 C terminus and exhibited antiproliferative activities against multiple tumor cells without inhibiting ATPase activity. Read More

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The rice RNase P protein subunit Rpp30 confers broad-spectrum resistance to fungal and bacterial pathogens.

Plant Biotechnol J 2021 May 1. Epub 2021 May 1.

State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.

RNase P functions either as a catalytic ribonucleoprotein (RNP) or as an RNA-free polypeptide to catalyze RNA processing, primarily tRNA 5' maturation. To the growing evidence of non-canonical roles for RNase P RNP subunits including regulation of chromatin structure and function, we add here a role for the rice RNase P Rpp30 in innate immunity. This protein (encoded by LOC_Os11g01074) was uncovered as the top hit in yeast two-hybrid assays performed with the rice histone deacetylase HDT701 as bait. Read More

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Characterization of a novel toll-like receptor and activation NF-κB signal pathway in triangle sail mussel Hyriopsis cumingii.

Comp Biochem Physiol B Biochem Mol Biol 2021 Apr 27;255:110608. Epub 2021 Apr 27.

College of Life Sciences, Department of Aquatic Sciences, Nanchang University, Nanchang 330031, China. Electronic address:

Toll-like receptor (TLR) family plays an important role in innate immunity for detection of and defense against microbial pathogens. In this study, a novel toll-like receptor (HcTLRn) was characterized from freshwater pearl mussel H. cumingii. Read More

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The C-terminal tail extension of myosin 16 possesses intrinsically disordered regions as molten globule and interacts with the N-terminal ankyrin.

J Biol Chem 2021 Apr 27:100716. Epub 2021 Apr 27.

Department of Biophysics, Medical School, University of Pécs, Pécs, H-7624, Hungary; Szentágothai Research Center, Pécs, H-7624, Hungary; MTA-PTE Nuclear-Mitochondrial Interactions Research Group, Pécs, H-7624, Hungary. Electronic address:

The lesser-known unconventional myosin 16 protein is essential in proper neuronal functioning and has been implicated in cell cycle regulation. Its longer Myo16b isoform contains a C-terminal tail extension (Myo16Tail), which has been shown to play a role in the neuronal phosphoinositide 3-kinase signaling pathway. Myo16Tail mediates the actin cytoskeleton remodeling, as well as downregulates the actin dynamics at the postsynaptic site of dendritic spines and involved in the organization of the presynaptic axon terminals. Read More

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Supercoiling Structure-Based Design of a Trimeric Coiled-Coil Peptide with High Potency against HIV-1 and Human β-Coronavirus Infection.

J Med Chem 2021 Apr 30. Epub 2021 Apr 30.

Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences & Shanghai Public Health Clinical Center, Fudan University, 130 Dong An Road, Shanghai 200032, China.

Hexameric structure formation through packing of three C-terminal helices and an N-terminal trimeric coiled-coil core has been proposed as a general mechanism of class I enveloped virus entry. In this process, the C-terminal helical repeat (HR2) region of viral membrane fusion proteins becomes transiently exposed and accessible to N-terminal helical repeat (HR1) trimer-based fusion inhibitors. Herein, we describe a mimetic of the HIV-1 gp41 HR1 trimer, N3G, as a promising therapeutic against HIV-1 infection. Read More

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The unusual structure of the PiggyMac cysteine-rich domain reveals zinc finger diversity in PiggyBac-related transposases.

Mob DNA 2021 Apr 29;12(1):12. Epub 2021 Apr 29.

Université Paris-Saclay, CNRS, Institut de Chimie des Substances Naturelles, UPR 2301, 1 Avenue de la Terrasse, 91198, Gif sur Yvette Cedex, France.

Background: Transposons are mobile genetic elements that colonize genomes and drive their plasticity in all organisms. DNA transposon-encoded transposases bind to the ends of their cognate transposons and catalyze their movement. In some cases, exaptation of transposon genes has allowed novel cellular functions to emerge. Read More

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Age, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohort.

Viruses 2021 04 28;13(5). Epub 2021 Apr 28.

Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa.

The COVID-19 pandemic has affected all individuals across the globe in some way. Despite large numbers of reported seroprevalence studies, there remains a limited understanding of how the magnitude and epitope utilization of the humoral immune response to SARS-CoV-2 viral anti-gens varies within populations following natural infection. Here, we designed a quantitative, multi-epitope protein microarray comprising various nucleocapsid protein structural motifs, including two structural domains and three intrinsically disordered regions. Read More

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Identification of a Chlorovirus PBCV-1 Protein Involved in Degrading the Host Cell Wall during Virus Infection.

Viruses 2021 Apr 28;13(5). Epub 2021 Apr 28.

Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583-0900, USA.

Chloroviruses are unusual among viruses infecting eukaryotic organisms in that they must, like bacteriophages, penetrate a rigid cell wall to initiate infection. PBCV-1 infects its host, NC64A by specifically binding to and degrading the cell wall of the host at the point of contact by a virus-packaged enzyme(s). However, PBCV-1 does not use any of the five previously characterized virus-encoded polysaccharide degrading enzymes to digest the host cell wall during virus entry because none of the enzymes are packaged in the virion. Read More

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Conserved Conformational Hierarchy across Functionally Divergent Glycosyltransferases of the GT-B Structural Superfamily as Determined from Microsecond Molecular Dynamics.

Int J Mol Sci 2021 Apr 28;22(9). Epub 2021 Apr 28.

Bioinformatics and Computational Biology Program, University of Minnesota, Minneapolis, MN 55455, USA.

It has long been understood that some proteins undergo conformational transitions en route to the Michaelis Complex to allow chemistry. Examination of crystal structures of glycosyltransferase enzymes in the GT-B structural class reveals that the presence of ligand in the active site triggers an open-to-closed conformation transition, necessary for their catalytic functions. Herein, we describe microsecond molecular dynamics simulations of two distantly related glycosyltransferases that are part of the GT-B structural superfamily, HepI and GtfA. Read More

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DCTN1 Binds to TDP-43 and Regulates TDP-43 Aggregation.

Int J Mol Sci 2021 Apr 13;22(8). Epub 2021 Apr 13.

Department of Neurology, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.

A common pathological hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis, is cytoplasmic mislocalization and aggregation of nuclear RNA-binding protein TDP-43. Perry disease, which displays inherited atypical parkinsonism, is a type of TDP-43 proteinopathy. The causative gene encodes the largest subunit of the dynactin complex. Read More

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Arpin Regulates Migration Persistence by Interacting with Both Tankyrases and the Arp2/3 Complex.

Int J Mol Sci 2021 Apr 16;22(8). Epub 2021 Apr 16.

CNRS UMR7654, Institut Polytechnique de Paris, 91120 Palaiseau, France.

During cell migration, protrusion of the leading edge is driven by the polymerization of Arp2/3-dependent branched actin networks. Migration persistence is negatively regulated by the Arp2/3 inhibitory protein Arpin. To better understand Arpin regulation in the cell, we looked for its interacting partners and identified both Tankyrase 1 and 2 (TNKS) using a yeast two-hybrid screening and coimmunoprecipitation with full-length Arpin as bait. Read More

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Substrate Specificity of Chimeric Enzymes Formed by Interchange of the Catalytic and Specificity Domains of the 5-Nucleotidase UshA and the 3-Nucleotidase CpdB.

Molecules 2021 Apr 16;26(8). Epub 2021 Apr 16.

Grupo de Enzimología, Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Medicina y Ciencias de la Salud, Universidad de Extremadura, 06006 Badajoz, Spain.

The 5'-nucleotidase UshA and the 3'-nucleotidase CpdB from are broad-specificity phosphohydrolases with similar two-domain structures. Their N-terminal domains (UshA_Ndom and CpdB_Ndom) contain the catalytic site, and their C-terminal domains (UshA_Cdom and CpdB_Cdom) contain a substrate-binding site responsible for specificity. Both enzymes show only partial overlap in their substrate specificities. Read More

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Extremely Thermostabilizing Core Mutations in Coiled-Coil Mimetic Proteins of HIV-1 gp41 Produce Diverse Effects on Target Binding but Do Not Affect Their Inhibitory Activity.

Biomolecules 2021 Apr 12;11(4). Epub 2021 Apr 12.

Departamento de Química Física, Instituto de Biotecnología, Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente (UEQ), Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain.

A promising strategy to neutralize HIV-1 is to target the gp41 spike subunit to block membrane fusion with the cell. We previously designed a series of single-chain proteins (named covNHR) that mimic the trimeric coiled-coil structure of the gp41 N-terminal heptad repeat (NHR) region and potently inhibit HIV-1 cell infection by avidly binding the complementary C-terminal heptad repeat (CHR) region. These proteins constitute excellent tools to understand the structural and thermodynamic features of this therapeutically important interaction. Read More

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