2,789 results match your criteria "coiled-coil" region

Conservation and Identity Selection of Cationic Residues Flanking the Hydrophobic Regions in Intermediate Filament Superfamily.

Front Chem 2021 2;9:752630. Epub 2021 Sep 2.

State Key Laboratory of Medical Molecular Biology, School of Basic Medicine Peking Union Medical College, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Beijing, China.

The interplay between the hydrophobic interactions generated by the nonpolar region and the proximal functional groups within nanometers of the nonpolar region offers a promising strategy to manipulate the intermolecular hydrophobic attractions in an artificial molecule system, but the outcomes of such modulations in the building of a native protein architecture remain unclear. Here we focus on the intermediate filament (IF) coiled-coil superfamily to assess the conservation of positively charged residue identity via a biostatistical approach. By screening the disease-correlated mutations throughout the IF superfamily, 10 distinct hotspots where a cation-to-cation substitution is associated with a pathogenic syndrome have been identified. Read More

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September 2021

NudCL2 is an autophagy receptor that mediates selective autophagic degradation of CP110 at mother centrioles to promote ciliogenesis.

Cell Res 2021 Sep 3. Epub 2021 Sep 3.

The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China.

Primary cilia extending from mother centrioles are essential for vertebrate development and homeostasis maintenance. Centriolar coiled-coil protein 110 (CP110) has been reported to suppress ciliogenesis initiation by capping the distal ends of mother centrioles. However, the mechanism underlying the specific degradation of mother centriole-capping CP110 to promote cilia initiation remains unknown. Read More

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September 2021

Comparative analysis of the MyTH4-FERM myosins reveals insights into the determinants of actin track selection in polarized epithelia.

Mol Biol Cell 2021 Sep 2:mbcE20070494. Epub 2021 Sep 2.

Department of Biological Sciences, University of Toledo, Toledo, Ohio 43606.

MyTH4-FERM (MF) myosins evolved to play a role in the creation and function of a variety of actin-based membrane protrusions that extend from cells. Here, we performed an analysis of the MF myosins, Myo7A, Myo7B, and Myo10, to gain insight into how they select for their preferred actin networks. Using enterocytes that create spatially separated actin tracks in the form of apical microvilli and basal filopodia, we show that actin track selection is principally guided by the mode of oligomerization of the myosin along with the identity of the motor domain, with little influence from the specific composition of the lever arm. Read More

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September 2021

ZC3HC1 Is a Novel Inherent Component of the Nuclear Basket, Resident in a State of Reciprocal Dependence with TPR.

Cells 2021 Jul 30;10(8). Epub 2021 Jul 30.

Max Planck Institute for Biophysical Chemistry, D-37077 Göttingen, Germany.

The nuclear basket (NB) scaffold, a fibrillar structure anchored to the nuclear pore complex (NPC), is regarded as constructed of polypeptides of the coiled-coil dominated protein TPR to which other proteins can bind without contributing to the NB's structural integrity. Here we report vertebrate protein ZC3HC1 as a novel inherent constituent of the NB, common at the nuclear envelopes (NE) of proliferating and non-dividing, terminally differentiated cells of different morphogenetic origin. Formerly described as a protein of other functions, we instead present the NB component ZC3HC1 as a protein required for enabling distinct amounts of TPR to occur NB-appended, with such ZC3HC1-dependency applying to about half the total amount of TPR at the NEs of different somatic cell types. Read More

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Intermediate Filaments from Tissue Integrity to Single Molecule Mechanics.

Cells 2021 Jul 27;10(8). Epub 2021 Jul 27.

Cell Polarity, Migration and Cancer Unit, Institut Pasteur, UMR3691 CNRS, Equipe Labellisée Ligue Contre le Cancer, F-75015 Paris, France.

Cytoplasmic intermediate filaments (IFs), which together with actin and microtubules form the cytoskeleton, are composed of a large and diverse family of proteins. Efforts to elucidate the molecular mechanisms responsible for IF-associated diseases increasingly point towards a major contribution of IFs to the cell's ability to adapt, resist and respond to mechanical challenges. From these observations, which echo the impressive resilience of IFs in vitro, we here discuss the role of IFs as master integrators of cell and tissue mechanics. Read More

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Decoding the role of coiled-coil motifs in human prion-like proteins.

Prion 2021 12;15(1):143-154

Institut De Biotecnologia I De Biomedicina (Ibb) and Departament De Bioquímica I Biologia Molecular, Universitat Autónoma De Barcelona, Barcelona, Spain.

Prions are self-propagating proteins that cause fatal neurodegenerative diseases in humans. However, increasing evidence suggests that eukaryotic cells exploit prion conformational conversion for functional purposes. A recent study delineated a group of twenty prion-like proteins in humans, characterized by the presence of low-complexity glutamine-rich sequences with overlapping coiled-coil (CCs) motifs. Read More

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December 2021

Whole exome sequencing reveals a homozygous C1QBP deletion as the cause of progressive external ophthalmoplegia and multiple mtDNA deletions.

Neuromuscul Disord 2021 Jul 4. Epub 2021 Jul 4.

School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, the Netherlands; Department of Toxicogenomics, Clinical Genomics Unit, Maastricht University, Maastricht, the Netherlands; School for Oncology and Developmental Biology (GROW), Maastricht University, Maastricht, the Netherlands. Electronic address:

Whole exome sequencing (WES), analyzed with GENESIS and WeGET, revealed a homozygous deletion in the C1QBP gene in a patient with progressive external ophthalmoplegia (PEO) and multiple mtDNA deletions. The gene encodes the mitochondria-located complementary 1 Q subcomponent-binding protein, involved in mitochondrial homeostasis. Biallelic mutations in C1QBP cause mitochondrial cardiomyopathy and/or PEO with variable age of onset. Read More

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The anti-parallel dimer binding interface in STAT3 transcription factor is required for the inactivation of cytokine-mediated signal transduction.

Biochim Biophys Acta Mol Cell Res 2021 Aug 12;1868(12):119118. Epub 2021 Aug 12.

Department of Psychosomatic Medicine and Psychotherapy, University Medical Centre Göttingen, German Centre for Cardiovascular Research (DZHK), partner site Göttingen, Germany. Electronic address:

Signal transducer and activator of transcription 3 (STAT3) gain-of-function mutations have been widely reported in patients with tumors and haematological malignancies. However, the molecular mechanisms of these pathogenic mutations remain largely uninvestigated. In this study, we have extensively characterized two STAT3 missense mutations, namely a valine-to-alanine exchange in the amino-terminal region (V77A) and a phenylalanine-to-alanine substitution (F174A) in the coiled-coil domain. Read More

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Structural and biochemical advances on the recruitment of the autophagy-initiating ULK and TBK1 complexes by autophagy receptor NDP52.

Sci Adv 2021 Aug 13;7(33). Epub 2021 Aug 13.

State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, China.

The recruitment of Unc-51-like kinase and TANK-binding kinase 1 complexes is essential for Nuclear dot protein 52-mediated selective autophagy and relies on the specific association of NDP52, RB1-inducible coiled-coil protein 1, and Nak-associated protein 1 (5-azacytidine-induced protein 2, AZI2). However, the underlying molecular mechanism remains elusive. Here, we find that except for the NDP52 SKIP carboxyl homology (SKICH)/RB1CC1 coiled-coil interaction, the LC3-interacting region of NDP52 can directly interact with the RB1CC1 Claw domain, as that of NAP1 FIP200-binding region (FIR). Read More

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Dimerization underlies the aggregation propensity of intrinsically disordered coiled-coil domain-containing 124.

Proteins 2021 Aug 8. Epub 2021 Aug 8.

Department of Radiotherapy and Oncology, University Hospital Frankfurt, Frankfurt am Main, Germany.

Coiled-coil domain-containing 124 (CCDC124) is a recently discovered ribosome-binding protein conserved in eukaryotes. CCDC124 has regulatory functions on the mediation of reversible ribosomal hibernation and translational recovery by direct attachment to large subunit ribosomal protein uL5, 25S rRNA backbone, and tRNA-binding P/A-site major groove. Moreover, it independently mediates cell division and cellular stress response by facilitating cytokinetic abscission and disulfide stress-dependent transcriptional regulation, respectively. Read More

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Crystal structure of the MyRF ICA domain with its upstream β-helical stalk reveals the molecular mechanisms underlying its trimerization and self-cleavage.

Int J Biol Sci 2021 13;17(11):2931-2943. Epub 2021 Jul 13.

State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fujian College, University of Chinese Academy of Sciences, 155 Yangqiao Road West, Fuzhou, 350002, China.

Myelin gene regulatory factor (MyRF), a novel membrane transcription factor expressed on the endoplasmic reticulum membrane, functions as a trimer. The trimerization of MyRF is associated with a fragment between the DNA binding domain and transmembrane domain that shares homology with the triple-β-helix and intramolecular chaperone autocleavage (ICA) domain of phage tailspike proteins. The molecular details of these domains in eukaryotes have not been elucidated. Read More

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Evaluation of FGFR targeting in breast cancer through interrogation of patient-derived models.

Breast Cancer Res 2021 08 3;23(1):82. Epub 2021 Aug 3.

Cancer Program, Monash Biomedicine Discovery Institute, Clayton, VIC, 3800, Australia.

Background: Particular breast cancer subtypes pose a clinical challenge due to limited targeted therapeutic options and/or poor responses to the existing targeted therapies. While cell lines provide useful pre-clinical models, patient-derived xenografts (PDX) and organoids (PDO) provide significant advantages, including maintenance of genetic and phenotypic heterogeneity, 3D architecture and for PDX, tumor-stroma interactions. In this study, we applied an integrated multi-omic approach across panels of breast cancer PDXs and PDOs in order to identify candidate therapeutic targets, with a major focus on specific FGFRs. Read More

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CCDC65 as a new potential tumor suppressor induced by metformin inhibits activation of AKT1 via ubiquitination of ENO1 in gastric cancer.

Theranostics 2021 13;11(16):8112-8128. Epub 2021 Jul 13.

Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, 510315 Guangzhou, China.

The coiled-coil domain containing protein members have been well documented for their roles in many diseases including cancers. However, the function of the coiled-coil domain containing 65 (CCDC65) remains unknown in tumorigenesis including gastric cancer. CCDC65 expression and its correlation with clinical features and prognosis of gastric cancer were analyzed in tissue. Read More

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Tail suspension delays ectopic ossification in proteoglycan-induced ankylosing spondylitis in mice via miR-103/DKK1.

Exp Ther Med 2021 Sep 7;22(3):965. Epub 2021 Jul 7.

Department of Rehabilitation Medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510000, P.R. China.

Ankylosing spondylitis (AS), characterized by inflammatory lesions and osteophyte formation, is a common immune rheumatic disease affecting the sacroiliac and axial joints. A high-intensity mechanical load is known to accelerate the heterotopic ossification associated with enthesitis in AS. Thus, the present study explored whether decreased mechanical load could delay the heterotopic ossification in AS. Read More

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September 2021

Homodimerization of a proximal region within the C-terminus of the orphan G-protein coupled receptor GPR179.

Neurochem Int 2021 Oct 30;149:105150. Epub 2021 Jul 30.

Institut für Biochemie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Fahrstrasse 17, 91054, Erlangen, Germany. Electronic address:

G-protein coupled receptors exhibit numerous biological functions. The orphan G-protein coupled receptor GPR179 is a central component of a 1 Megadalton large signalling complex in the ON-pathway of the mammalian retina that assembles multiple proteins, including the metabotropic glutamate receptor mGluR6. Dimer formation is a hallmark of G-protein coupled receptors and some use intracellular C-termini for dimerization. Read More

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October 2021

Coiled-coil binding of the leucine zipper domains of APOL1 is necessary for the open cation channel conformation.

J Biol Chem 2021 Jul 28:101009. Epub 2021 Jul 28.

Department of Biological sciences, Hunter College, City University of New York, USA. Electronic address:

Apolipoprotein L-I (APOL1) is a channel-forming component necessary for innate immunity. The common human APOL1 variant G0 provides protection against infection with certain Trypanosoma and Leishmania parasite species, but it cannot protect against the trypanosomes responsible for human African trypanosomiasis (HAT). Human APOL1 variants G1 and G2 protect against human-infective trypanosomes, but also confer a higher risk of developing chronic kidney disease. Read More

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Structure of the human C9orf72-SMCR8 complex reveals a multivalent protein interaction architecture.

PLoS Biol 2021 Jul 23;19(7):e3001344. Epub 2021 Jul 23.

Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.

A major cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) spectrum disorder is the hexanucleotide G4C2 repeat expansion in the first intron of the C9orf72 gene. Many underlying mechanisms lead to manifestation of disease that include toxic gain-of-function by repeat G4C2 RNAs, dipeptide repeat proteins, and a reduction of the C9orf72 gene product. The C9orf72 protein interacts with SMCR8 and WDR41 to form a trimeric complex and regulates multiple cellular pathways including autophagy. Read More

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Calponin-homology domain mediated bending of membrane-associated actin filaments.

Elife 2021 07 16;10. Epub 2021 Jul 16.

Centre for Mechanochemical Cell Biology and Warwick Medical School, Division of Biomedical Sciences, Coventry, United Kingdom.

Actin filaments are central to numerous biological processes in all domains of life. Driven by the interplay with molecular motors, actin binding and actin modulating proteins, the actin cytoskeleton exhibits a variety of geometries. This includes structures with a curved geometry such as axon-stabilizing actin rings, actin cages around mitochondria and the cytokinetic actomyosin ring, which are generally assumed to be formed by short linear filaments held together by actin cross-linkers. Read More

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Mandibular muscle troponin of the Florida carpenter ant Camponotus floridanus: extending our insights into invertebrate Ca regulation.

J Muscle Res Cell Motil 2021 06 13;42(2):399-417. Epub 2021 Jul 13.

Department of Biological Science, Florida State University, Tallahassee, FL, 32306, USA.

Ants use their mandibles for a variety of functions and behaviors. We investigated mandibular muscle structure and function from major workers of the Florida carpenter ant Camponotus floridanus: force-pCa relation and velocity of unloaded shortening of single, permeabilized fibres, primary sequences of troponin subunits (TnC, TnI and TnT) from a mandibular muscle cDNA library, and muscle fibre ultrastructure. From the mechanical measurements, we found Ca-sensitivity of isometric force was markedly shifted rightward compared with vertebrate striated muscle. Read More

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RAB7 activity is required for the regulation of mitophagy in oocyte meiosis and oocyte quality control during ovarian aging.

Autophagy 2021 Jul 7:1-18. Epub 2021 Jul 7.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.

There is increasing evidence that mitophagy, a specialized form of autophagy to degrade and clear long-lived or damaged mitochondria, is impaired in aging and age-related disease. Previous study has demonstrated the obesity-exposed oocytes accumulate and transmit damaged mitochondria due to an inability to activate mitophagy. However, it remains unknown whether mitophagy functions in oocyte and what's the regulatory mechanism in oocyte aging. Read More

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Secondary Structure of the Novel Myosin Binding Domain WYR and Implications within Myosin Structure.

Biology (Basel) 2021 Jun 29;10(7). Epub 2021 Jun 29.

Department of Biology, University of Vermont, Burlington, VT 05405, USA.

Structural changes in the myosin II light meromyosin (LMM) that influence thick filament mechanical properties and muscle function are modulated by LMM-binding proteins. Flightin is an LMM-binding protein indispensable for the function of Drosophila indirect flight muscle (IFM). Flightin has a three-domain structure that includes WYR, a novel 52 aa domain conserved throughout Pancrustacea. Read More

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High Conformational Flexibility of the E2F1/DP1/DNA Complex.

J Mol Biol 2021 Sep 25;433(18):167119. Epub 2021 Jun 25.

Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy. Electronic address:

The E2F1 transcription factor is a master regulator of cell-cycle progression whose uncontrolled activation contributes to tumor cells growth. E2F1 binds DNA as a heterodimer with DP partners, resulting in a multi-domain quaternary-structure complex composed of DNA binding domains, a coiled coil domain and a marked box domain separated by short linkers. Building on the 3D knowledge of the single domains of E2F and DPs, we characterized the structure and dynamics of the complete E2F1/DP1/DNA complex by a combination of small-angle X-ray scattering and molecular dynamics simulations. Read More

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September 2021

Molecular characterization, dynamic transcription, and potential function of KIF3A/KIF3B during spermiogenesis in Opsariichthys bidens.

Gene 2021 Sep 24;798:145795. Epub 2021 Jun 24.

Key Laboratory of Applied Marine Biotechnology by the Ministry of Education, School of Marine Sciences, Ningbo University, Ningbo, Zhejiang 315211, People's Republic of China. Electronic address:

Spermiogenesis is the final phase of spermatogenesis, wherein the spermatids differentiate into mature spermatozoa via complex morphological transformation. In this process, kinesin plays an important role. Here, we observed the morphological transformation of spermatids and analyzed the characterization, dynamic transcription, and potential function of kinesin KIF3A/KIF3B during spermiogenesis in Chinese hook snout carp (Opsariichthys bidens). Read More

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September 2021

The MLKL kinase-like domain dimerization is an indispensable step of mammalian MLKL activation in necroptosis signaling.

Cell Death Dis 2021 06 22;12(7):638. Epub 2021 Jun 22.

School of Life Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai, 201210, China.

MLKL phosphorylation by RIP3 is the commitment step of necroptosis execution, which could induce MLKL activation featured as MLKL monomer-oligomer transition. Here, we reported that the dimerization of the MLKL kinase-like domain was the direct consequence of RIP3 triggered MLKL-phosphorylation. Two inter-dimer interfaces were found in the crystal structure of human MLKL. Read More

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Synthetic fluorescent MYC probe: Inhibitor binding site elucidation and development of a high-throughput screening assay.

Bioorg Med Chem 2021 Jul 6;42:116246. Epub 2021 Jun 6.

Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, United States. Electronic address:

We report the discovery of a fluorescent small molecule probe. This probe exhibits an emission increase in the presence of the oncoprotein MYC that can be attenuated by a competing inhibitor. Hydrogen-deuterium exchange mass spectrometry analysis, rationalized by induced-fit docking, suggests it binds to the "coiled-coil" region of the leucine zipper domain. Read More

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The plant nuclear lamina proteins NMCP1 and NMCP2 form a filamentous network with lateral filament associations.

J Exp Bot 2021 Jun 4. Epub 2021 Jun 4.

Laboratory of Crop Physiology, Research Faculty of Agriculture, Hokkaido University.

Plant genomes lack genes encoding intermediate filament proteins, including lamins; however, functional lamin analogues are presumed to exist in plants. Plant-specific coiled-coil proteins, that is, nuclear matrix constituent proteins (NMCPs), are the most likely candidates as the structural elements of the nuclear lamina (NL) because they exhibit a lamin-like domain arrangement, are exclusively localised at the nuclear periphery, and have functions that are analogous to those of lamins. However, their assembly into filamentous polymers has not yet been confirmed. Read More

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Circ-ACAP2 facilitates the progression of colorectal cancer through mediating miR-143-3p/FZD4 axis.

Eur J Clin Invest 2021 Jun 4:e13607. Epub 2021 Jun 4.

Department of Oncology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian, P.R. China.

Background: Circular RNAs (circRNAs) play crucial roles in multiple cancers, including colorectal cancer (CRC). Here, we explored the role of circRNA ArfGAP with coiled-coil, ankyrin repeat and PH domains 2 (circ-ACAP2) in the progression and radioresistance of CRC.

Methods: Quantitative real-time polymerase chain reaction (qPCR) and Western blot assay were used to detect RNA and protein expression, respectively. Read More

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Cell adhesion factors in the orbitofrontal cortex control cue-induced reinstatement of cocaine seeking and amygdala-dependent goal seeking.

J Neurosci 2021 May 27. Epub 2021 May 27.

Departments of Pediatrics and Psychiatry, Emory University School of Medicine, United States

Repeated cocaine exposure causes dendritic spine loss in the orbitofrontal cortex, which might contribute to poor orbitofrontal cortical function following drug exposure. One challenge, however, has been verifying links between neuronal structural plasticity and behavior, if any. Here we report that cocaine self-administration triggers the loss of dendritic spines on excitatory neurons in the orbitofrontal cortex of male and female mice (as has been reported in rats). Read More

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Molecular Dynamic Simulations Suggest That Metabolite-Induced Post-Translational Modifications Alter the Behavior of the Fibrinogen Coiled-Coil Domain.

Metabolites 2021 May 11;11(5). Epub 2021 May 11.

Department of Biochemistry, Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 00 Prague, Czech Republic.

Fibrinogen is an abundant blood plasma protein that, inter alia, participates in blood coagulation. It polymerizes to form a fibrin clot that is among the major components of the thrombus. Fibrinogen reactions with various reactive metabolites may induce post-translational modifications (PTMs) into the protein structure that affect the architecture and properties of fibrin clots. Read More

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RLIP76: A Structural and Functional Triumvirate.

Cancers (Basel) 2021 May 4;13(9). Epub 2021 May 4.

Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.

RLIP76/RalBP1 is an ATP-dependent transporter of glutathione conjugates, which is overexpressed in various human cancers, but its diverse functions in normal cells, which include endocytosis, stress response and mitochondrial dynamics, are still not fully understood. The protein can be divided into three distinct regions, each with its own structural properties. At the centre of the protein are two well-defined domains, a GTPase activating protein domain targeting Rho family small G proteins and a small coiled-coil that binds to the Ras family small GTPases RalA and RalB. Read More

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