182 results match your criteria lc8

Structural characterization of the self-association domain of swallow.

Protein Sci 2021 May 9;30(5):1056-1063. Epub 2021 Mar 9.

Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon, USA.

Swallow, a 62 kDa multidomain protein, is required for the proper localization of several mRNAs involved in the development of Drosophila oocytes. The dimerization of Swallow depends on a 71-residue self-association domain in the center of the protein sequence, and is significantly stabilized by a binding interaction with dynein light chain (LC8). Here, we detail the use of solution-state nuclear magnetic resonance spectroscopy to characterize the structure of this self-association domain, thereby establishing that this domain forms a parallel coiled-coil and providing insight into how the stability of the dimerization interaction is regulated. Read More

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Crystal structure of human LC8 bound to a peptide from Ebola virus VP35.

J Microbiol 2021 Apr 25;59(4):410-416. Epub 2021 Feb 25.

Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea.

Zaire ebolavirus, commonly called Ebola virus (EBOV), is an RNA virus that causes severe hemorrhagic fever with high mortality. Viral protein 35 (VP35) is a virulence factor encoded in the EBOV genome. VP35 inhibits host innate immune responses and functions as a critical cofactor for viral RNA replication. Read More

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Molecular principles of Piwi-mediated cotranscriptional silencing through the dimeric SFiNX complex.

Genes Dev 2021 Mar 11;35(5-6):392-409. Epub 2021 Feb 11.

Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), 1030 Vienna, Austria.

Nuclear Argonaute proteins, guided by their bound small RNAs to nascent target transcripts, mediate cotranscriptional silencing of transposons and repetitive genomic loci through heterochromatin formation. The molecular mechanisms involved in this process are incompletely understood. Here, we show that the SFiNX complex, a silencing mediator downstream from nuclear Piwi-piRNA complexes in , facilitates cotranscriptional silencing as a homodimer. Read More

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Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in .

Elife 2021 Feb 4;10. Epub 2021 Feb 4.

Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.

In animal gonads, the PIWI-interacting RNA (piRNA) pathway guards genome integrity in part through the co-transcriptional gene silencing of transposon insertions. In ovaries, piRNA-loaded Piwi detects nascent transposon transcripts and instructs heterochromatin formation through the anoramix-nduced o-ranscriptional ilencing (PICTS) complex, containing Panoramix, Nxf2 and Nxt1. Here, we report that the highly conserved dynein light chain LC8/Cut-up (Ctp) is an essential component of the PICTS complex. Read More

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February 2021

Numerical magnitude, rather than individual bias, explains spatial numerical association in newborn chicks.

Elife 2020 06 25;9. Epub 2020 Jun 25.

Department of General Psychology, University of Padova, Padova, Italy.

We associate small numbers with the left and large numbers with the right side of space. Recent evidence from human newborns and non-human animals has challenged the primary role assigned to culture, in determining this spatial numerical association (SNA). Nevertheless, the effect of individual spatial biases has not been considered in previous research. Read More

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Emerging Features of Linear Motif-Binding Hub Proteins.

Trends Biochem Sci 2020 05 20;45(5):375-384. Epub 2020 Feb 20.

Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA. Electronic address:

Hub proteins are important elements of interactomes within an organism; they bind diverse partners, display significant pleiotropy, and connect many cellular systems. Static hubs interact with their partners simultaneously, while dynamic hubs bind different partners at different locations and times. Although this distinguishes some features of hub protein/partner interactions, the increasing literature requires an expanded categorization of molecular and functional properties. Read More

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KIF5A-dependent axonal transport deficiency disrupts autophagic flux in trimethyltin chloride-induced neurotoxicity.

Autophagy 2021 Apr 30;17(4):903-924. Epub 2020 Mar 30.

Department of Environmental Medicine, and Department of Emergency Medicine of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Trimethyltin chloride (TMT) is widely used as a constituent of fungicides and plastic stabilizers in the industrial and agricultural fields, and is generally acknowledged to have potent neurotoxicity, especially in the hippocampus; however, the mechanism of induction of neurotoxicity by TMT remains elusive. Herein, we exposed Neuro-2a cells to different concentrations of TMT (2, 4, and 8 μM) for 24 h. Proteomic analysis, coupled with bioinformatics analysis, revealed the important role of macroautophagy/autophagy-lysosome machinery in TMT-induced neurotoxicity. Read More

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The dynein light chain 8 (LC8) binds predominantly "in-register" to a multivalent intrinsically disordered partner.

J Biol Chem 2020 04 5;295(15):4912-4922. Epub 2020 Mar 5.

Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331

Dynein light chain 8 (LC8) interacts with intrinsically disordered proteins (IDPs) and influences a wide range of biological processes. It is becoming apparent that among the numerous IDPs that interact with LC8, many contain multiple LC8-binding sites. Although it is established that LC8 forms parallel IDP duplexes with some partners, such as nucleoporin Nup159 and dynein intermediate chain, the molecular details of these interactions and LC8's interactions with other diverse partners remain largely uncharacterized. Read More

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The LC8-RavP ensemble Structure Evinces A Role for LC8 in Regulating Lyssavirus Polymerase Functionality.

J Mol Biol 2019 12 18;431(24):4959-4977. Epub 2019 Oct 18.

From the Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA. Electronic address:

The rabies and Ebola viruses recruit the highly conserved host protein LC8 for their own reproductive success. In vivo knockouts of the LC8 recognition motif within the rabies virus phosphoprotein (RavP) result in completely nonlethal viral infections. In this work, we examine the molecular role LC8 plays in viral lethality. Read More

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December 2019

Interactions between two regulatory proteins of microtubule dynamics, HDAC6, TPPP/p25, and the hub protein, DYNLL/LC8.

Biochim Biophys Acta Mol Cell Res 2019 12 7;1866(12):118556. Epub 2019 Sep 7.

Institute of Enzymology, Research Center for Natural Sciences, Hungarian Academy of Sciences, Budapest 1117, Hungary. Electronic address:

Degradation of unwanted proteins is important in protein quality control cooperating with the dynein/dynactin-mediated trafficking along the acetylated microtubule (MT) network. Proteins associated directly/indirectly with tubulin/MTs play crucial roles in both physiological and pathological processes. Our studies focus on the interrelationship of the tubulin deacetylase HDAC6, the MT-associated TPPP/p25 with its deacetylase inhibitory potency and the hub dynein light chain DYNLL/LC8, constituent of dynein and numerous other protein complexes. Read More

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December 2019

Structure of the dynein-2 complex and its assembly with intraflagellar transport trains.

Nat Struct Mol Biol 2019 09 26;26(9):823-829. Epub 2019 Aug 26.

Institute of Structural and Molecular Biology, Birkbeck, University of London, London, UK.

Dynein-2 assembles with polymeric intraflagellar transport (IFT) trains to form a transport machinery that is crucial for cilia biogenesis and signaling. Here we recombinantly expressed the ~1.4-MDa human dynein-2 complex and solved its cryo-EM structure to near-atomic resolution. Read More

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September 2019

Systematic identification of recognition motifs for the hub protein LC8.

Life Sci Alliance 2019 08 2;2(4). Epub 2019 Jul 2.

Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR, USA

Hub proteins participate in cellular regulation by dynamic binding of multiple proteins within interaction networks. The hub protein LC8 reversibly interacts with more than 100 partners through a flexible pocket at its dimer interface. To explore the diversity of the LC8 partner pool, we screened for LC8 binding partners using a proteomic phage display library composed of peptides from the human proteome, which had no bias toward a known LC8 motif. Read More

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Dynll1 is essential for development and promotes endochondral bone formation by regulating intraflagellar dynein function in primary cilia.

Hum Mol Genet 2019 08;28(15):2573-2588

St. Vincent's Institute of Medical Research.

Mutations in subunits of the cilia-specific cytoplasmic dynein-2 (CD2) complex cause short-rib thoracic dystrophy syndromes (SRTDs), characterized by impaired bone growth and life-threatening perinatal respiratory complications. Different SRTD mutations result in varying disease severities. It remains unresolved whether this reflects the extent of retained hypomorphic protein functions or relative importance of the affected subunits for the activity of the CD2 holoenzyme. Read More

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LC8/DYNLL1 is a 53BP1 effector and regulates checkpoint activation.

Nucleic Acids Res 2019 07;47(12):6236-6249

Department of Radiation Oncology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

The tumor suppressor protein 53BP1 plays key roles in response to DNA double-strand breaks (DSBs) by serving as a master scaffold at the damaged chromatin. Current evidence indicates that 53BP1 assembles a cohort of DNA damage response (DDR) factors to distinctly execute its repertoire of DSB responses, including checkpoint activation and non-homologous end joining (NHEJ) repair. Here, we have uncovered LC8 (a. Read More

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Effects of laboratory capabilities on combating antimicrobial resistance, 2013-2016: A static model panel data analysis.

J Glob Antimicrob Resist 2019 12 20;19:116-121. Epub 2019 Mar 20.

School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:

Objectives: Antimicrobial resistance (AMR) has become a serious global public health problem. The World Health Organization (WHO) and European Union (EU) have taken actions to combat this issue, in which laboratory capability construction is a crucial part. This study aimed to explore the relationship between laboratory capabilities and antimicrobial resistance from a macro perspective. Read More

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December 2019

GLCCI1 is a novel protector against glucocorticoid-induced apoptosis in T cells.

FASEB J 2019 06 12;33(6):7387-7402. Epub 2019 Mar 12.

Department of Pediatrics, Kyorin University School of Medicine, Tokyo, Japan.

Glucocorticoids (GCs) potently induce T-cell apoptosis in a GC receptor (GR)-dependent manner and are used to control lymphocyte function in clinical practice. However, its downstream pathways remain controversial. Here, we showed that GC-induced transcript 1 (GLCCI1) is a novel downstream molecule of the GC-GR cascade that acts as an antiapoptotic mediator in thymic T cells. Read More

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Neospora caninum cytoplasmic dynein LC8 light chain 2 (NcDYNLL2) is differentially produced by pathogenically distinct isolates and regulates the host immune response.

Parasitology 2018 Dec 18:1-8. Epub 2018 Dec 18.

Animal Parasitic Diseases Laboratory, Agricultural Research Service, USDA,Beltsville, MD 20705,USA.

Neospora caninum is the causative agent of bovine neosporosis. A N. caninum cytoplasmic dynein LC8 light chain (NcDYNLL) protein was characterized in this study. Read More

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December 2018

Caenorhabditis elegans DLC-1 associates with ribonucleoprotein complexes to promote mRNA regulation.

FEBS Lett 2018 11 24;592(22):3683-3695. Epub 2018 Oct 24.

Division of Biological Sciences, University of Montana, Missoula, MT, USA.

Ribonucleoprotein complexes, which contain mRNAs and their regulator proteins, carry out post-transcriptional control of gene expression. The function of many RNA-binding proteins depends on their association with cofactors. Here, we use a genomic approach to identify transcripts associated with DLC-1, a protein previously identified as a cofactor of two unrelated RNA-binding proteins that act in the Caenorhabditis elegans germline. Read More

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November 2018

Assessment of the lethal and sublethal effects by spinetoram on cotton bollworm.

PLoS One 2018 14;13(9):e0204154. Epub 2018 Sep 14.

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

Helicoverpa armigera is an universal pest around the world, which has recovered again in recent years because of the adjustment of cropping structure and resistance to Bacillus thuringiensis (Bt) in China. As a new insecticide spinetoram is extensively used to control many pest insects, including H. armigera. Read More

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The established and the predicted roles of dynein light chain in the regulation of mitochondrial apoptosis.

Cell Cycle 2018 18;17(9):1037-1047. Epub 2018 Jul 18.

a Institute of Medical Microbiology and Hygiene, Faculty of Medicine , Medical Center-University of Freiburg , Freiburg , Germany.

The mitochondrial pathway of apoptosis is regulated by the interplay between the members of Bcl-2 family. Within this family, BH3-only proteins are the sensors of apoptotic stimuli and can trigger apoptosis either by inhibiting the anti-apoptotic Bcl-2-family proteins or by directly activating the effectors Bax and Bak. An expanding body of research suggests that a number of non-Bcl-2 proteins can also interact with Bcl-2 proteins and contribute to the decision of cell fate. Read More

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December 2019

APC2 controls dendrite development by promoting microtubule dynamics.

Nat Commun 2018 07 17;9(1):2773. Epub 2018 Jul 17.

Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.

Mixed polarity microtubule organization is the signature characteristic of vertebrate dendrites. Oppositely oriented microtubules form the basis for selective cargo trafficking in neurons, however the mechanisms that establish and maintain this organization are unclear. Here, we show that APC2, the brain-specific homolog of tumor-suppressor protein adenomatous polyposis coli (APC), promotes dynamics of minus-end-out microtubules in dendrites. Read More

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Multivalency regulates activity in an intrinsically disordered transcription factor.

Elife 2018 05 1;7. Epub 2018 May 1.

Department of Biochemistry and Biophysics, Oregon State University, Oregon, United States.

The transcription factor ASCIZ (ATMIN, ZNF822) has an unusually high number of recognition motifs for the product of its main target gene, the hub protein LC8 (DYNLL1). Using a combination of biophysical methods, structural analysis by NMR and electron microscopy, and cellular transcription assays, we developed a model that proposes a concerted role of intrinsic disorder and multiple LC8 binding events in regulating LC8 transcription. We demonstrate that the long intrinsically disordered C-terminal domain of ASCIZ binds LC8 to form a dynamic ensemble of complexes with a gradient of transcriptional activity that is inversely proportional to LC8 occupancy. Read More

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Backbone amide N chemical shift tensors report on hydrogen bonding interactions in proteins: A magic angle spinning NMR study.

Solid State Nucl Magn Reson 2018 08 15;92:1-6. Epub 2018 Mar 15.

Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, United States; Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh, Pittsburgh, PA 15260, United States. Electronic address:

Chemical shift tensors (CSTs) are an exquisite probe of local geometric and electronic structure. N CST are very sensitive to hydrogen bonding, yet they have been reported for very few proteins to date. Here we present experimental results and statistical analysis of backbone amide N CSTs for 100 residues of four proteins, two E. Read More

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Novel linear motif filtering protocol reveals the role of the LC8 dynein light chain in the Hippo pathway.

PLoS Comput Biol 2017 12 14;13(12):e1005885. Epub 2017 Dec 14.

MTA-ELTE Lendület Bioinformatics Research Group, Department of Biochemistry, Eötvös Loránd University, Budapest, Hungary.

Protein-protein interactions (PPIs) formed between short linear motifs and globular domains play important roles in many regulatory and signaling processes but are highly underrepresented in current protein-protein interaction databases. These types of interactions are usually characterized by a specific binding motif that captures the key amino acids shared among the interaction partners. However, the computational proteome-level identification of interaction partners based on the known motif is hindered by the huge number of randomly occurring matches from which biologically relevant motif hits need to be extracted. Read More

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December 2017

Dynein light chain regulates adaptive and innate B cell development by distinctive genetic mechanisms.

PLoS Genet 2017 Sep 18;13(9):e1007010. Epub 2017 Sep 18.

Molecular Genetics Unit, St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.

Mechanistic differences in the development and function of adaptive, high-affinity antibody-producing B-2 cells and innate-like, "natural" antibody-producing B-1a cells remain poorly understood. Here we show that the multi-functional dynein light chain (DYNLL1/LC8) plays important roles in the establishment of B-1a cells in the peritoneal cavity and in the ongoing development of B-2 lymphoid cells in the bone marrow of mice. Epistasis analyses indicate that Dynll1 regulates B-1a and early B-2 cell development in a single, linear pathway with its direct transcriptional activator ASCIZ (ATMIN/ZNF822), and that the two genes also have complementary functions during late B-2 cell development. Read More

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September 2017

Peptides mediating DNA transport on microtubules and their impact on non-viral gene transfer efficiency.

Biosci Rep 2017 Oct 17;37(5). Epub 2017 Oct 17.

Centre de Biophysique Moléculaire, CNRS UPR4301 and University of Orléans, Orléans 45071, cedex 02, France

Synthetic vectors such as cationic polymers and cationic lipids remain attractive tools for non-viral gene transfer which is a complex process whose effectiveness relies on the ability to deliver a plasmid DNA (pDNA) into the nucleus of non-dividing cells. Once in the cytosol, the transport of pDNAs towards the nuclear envelope is strongly impaired by their very low cytosolic mobility due to their large size. To promote their movement towards the cell nucleus, few strategies have been implemented to exploit dynein, the microtubule's (MT's) motor protein, for propagation of cytosolic pDNA along the MTs towards the cell nucleus. Read More

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October 2017

The LC8 homolog specifies the axonal transport of proteasomes.

J Cell Sci 2017 Oct 14;130(19):3388-3398. Epub 2017 Aug 14.

The Barshop Institute for Longevity and Aging Studies, Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA

Because of their functional polarity and elongated morphologies, microtubule-based transport of proteins and organelles is critical for normal neuronal function. The proteasome is required throughout the neuron for the highly regulated degradation of a broad set of protein targets whose functions underlie key physiological responses, including synaptic plasticity and axonal degeneration. Molecularly, the relationship between proteasome transport and the transport of the targets of proteasomes is unclear. Read More

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October 2017

The LC8 Recognition Motif Preferentially Samples Polyproline II Structure in Its Free State.

Biochemistry 2017 09 23;56(35):4656-4666. Epub 2017 Aug 23.

Department of Biochemistry and Biophysics, Oregon State University , Corvallis, Oregon 97331, United States.

LC8 is a ubiquitous hub protein that binds intrinsically disordered proteins and promotes their assembly into higher-order complexes. A common feature among the more than 100 essential LC8 binding proteins is that in the 10-12-amino acid recognition sequence there is a conserved QT motif but variable amino acids N- and C-terminal to the QT pair. The sequence diversity among LC8 binding partners implies that structural factors also contribute to specificity. Read More

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September 2017

Centriole translocation and degeneration during ciliogenesis in neurons.

EMBO J 2017 09 25;36(17):2553-2566. Epub 2017 Jul 25.

Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing, China

Neuronal cilia that are formed at the dendritic endings of sensory neurons are essential for sensory perception. However, it remains unclear how the centriole-derived basal body is positioned to form a template for cilium formation. Using fluorescence time-lapse microscopy, we show that the centriole translocates from the cell body to the dendrite tip in the sensory neurons. Read More

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September 2017