106 results match your criteria binding 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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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

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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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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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

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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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

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

Dynein light chain DLC-1 promotes localization and function of the PUF protein FBF-2 in germline progenitor cells.

Development 2016 12 18;143(24):4643-4653. Epub 2016 Nov 18.

Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA

PUF family translational repressors are conserved developmental regulators, but the molecular function provided by the regions flanking the PUF RNA-binding domain is unknown. In C. elegans, the PUF proteins FBF-1 and FBF-2 support germline progenitor maintenance by repressing production of meiotic proteins and use distinct mechanisms to repress their target mRNAs. Read More

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December 2016

Dynein light chain DYNLL1 subunit facilitates porcine circovirus type 2 intracellular transports along microtubules.

Arch Virol 2017 Mar 17;162(3):677-686. Epub 2016 Nov 17.

Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Kasetsart University, 50 Ngamwongwan Rd., Chatuchak, Bangkok, 10900, Thailand.

Microtubule (MT) and dynein motor proteins facilitate intracytoplasmic transport of cellular proteins. Various viruses utilize microtubules and dynein for their movement from the cell periphery to the nucleus. The aim of this study was to investigate the intracellular transport of porcine circovirus type 2 (PCV2) via 8 kDa dynein light chain (DYNLL1, LC8) subunit along the MTs. Read More

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Inverse regulation of two classic Hippo pathway target genes in Drosophila by the dimerization hub protein Ctp.

Sci Rep 2016 Mar 14;6:22726. Epub 2016 Mar 14.

Department of Cell Biology, Graduate Program in Biochemistry, Cell and Developmental Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.

The LC8 family of small ~8 kD proteins are highly conserved and interact with multiple protein partners in eukaryotic cells. LC8-binding modulates target protein activity, often through induced dimerization via LC8:LC8 homodimers. Although many LC8-interactors have roles in signaling cascades, LC8's role in developing epithelia is poorly understood. Read More

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The protein inhibitor of nNOS (PIN/DLC1/LC8) binding does not inhibit the NADPH-dependent heme reduction in nNOS, a key step in NO synthesis.

Biochem Biophys Res Commun 2016 Mar 26;472(1):189-93. Epub 2016 Feb 26.

Tata Institute of Fundamental Research (TIFR), Homi Bhabha Road, Mumbai 400 005, India. Electronic address:

The neuronal nitric oxide synthase (nNOS) is an essential enzyme involved in the synthesis of nitric oxide (NO), a potent neurotransmitter. Although previous studies have indicated that the dynein light chain 1 (DLC1) binding to nNOS could inhibit the NO synthesis, the claim is challenged by contradicting reports. Thus, the mechanism of nNOS regulation remained unclear. Read More

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The Anchored Flexibility Model in LC8 Motif Recognition: Insights from the Chica Complex.

Biochemistry 2016 Jan 22;55(1):199-209. Epub 2015 Dec 22.

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

LC8 is a dimeric hub protein involved in a large number of interactions central to cell function. It binds short linear motifs--usually containing a Thr-Gln-Thr (TQT) triplet--in intrinsically disordered regions of its binding partners, some of which have several LC8 recognition motifs in tandem. Hallmarks of the 7-10 amino acid motif are a high variability of LC8 binding affinity and extensive sequence permutation outside the TQT triplet. Read More

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January 2016

Dynein Light Chain LC8 Is Required for RNA Polymerase I-Mediated Transcription in Trypanosoma brucei, Facilitating Assembly and Promoter Binding of Class I Transcription Factor A.

Mol Cell Biol 2016 Jan 12;36(1):95-107. Epub 2015 Oct 12.

Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, Connecticut, USA

Dynein light chain LC8 is highly conserved among eukaryotes and has both dynein-dependent and dynein-independent functions. Interestingly, LC8 was identified as a subunit of the class I transcription factor A (CITFA), which is essential for transcription by RNA polymerase I (Pol I) in the parasite Trypanosoma brucei. Given that LC8 has never been identified with a basal transcription factor and that T. Read More

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January 2016

Interactions of Yeast Dynein with Dynein Light Chain and Dynactin: GENERAL IMPLICATIONS FOR INTRINSICALLY DISORDERED DUPLEX SCAFFOLDS IN MULTIPROTEIN ASSEMBLIES.

J Biol Chem 2015 Sep 7;290(39):23863-74. Epub 2015 Aug 7.

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

Intrinsically disordered protein (IDP) duplexes composed of two IDP chains cross-linked by bivalent partner proteins form scaffolds for assembly of multiprotein complexes. The N-terminal domain of dynein intermediate chain (N-IC) is one such IDP that forms a bivalent scaffold with multiple dynein light chains including LC8, a hub protein that promotes duplex formation of diverse IDP partners. N-IC also binds a subunit of the dynein regulator, dynactin. Read More

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September 2015

Multivalent IDP assemblies: Unique properties of LC8-associated, IDP duplex scaffolds.

FEBS Lett 2015 Sep 29;589(19 Pt A):2543-51. Epub 2015 Jul 29.

Department of Biochemistry & Biophysics, Oregon State University, Corvallis, OR 97331, United States. Electronic address:

A wide variety of subcellular complexes are composed of one or more intrinsically disordered proteins (IDPs) that are multivalent, flexible, and characterized by dynamic binding of diverse partner proteins. These multivalent IDP assemblies, of broad functional diversity, are classified here into five categories distinguished by the number of IDP chains and the arrangement of partner proteins in the functional complex. Examples of each category are summarized in the context of the exceptional molecular and biological properties of IDPs. Read More

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September 2015

Ebola virus VP35 interaction with dynein LC8 regulates viral RNA synthesis.

J Virol 2015 May 4;89(9):5148-53. Epub 2015 Mar 4.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA

Ebola virus VP35 inhibits alpha/beta interferon production and functions as a viral polymerase cofactor. Previously, the 8-kDa cytoplasmic dynein light chain (LC8) was demonstrated to interact with VP35, but the functional consequences were unclear. Here we demonstrate that the interaction is direct and of high affinity and that binding stabilizes the VP35 N-terminal oligomerization domain and enhances viral RNA synthesis. Read More

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Molecular handoffs in nitrergic neurotransmission.

Authors:
Arun Chaudhury

Front Med (Lausanne) 2014 10;1. Epub 2014 Apr 10.

Department of Surgery, Brigham and Women's Hospital, Harvard Medical School and VA Boston Healthcare System , Boston, MA , USA.

Postsynaptic density (PSD) proteins in excitatory synapses are relatively immobile components, while there is a structured organization of mobile scaffolding proteins lying beneath the PSDs. For example, shank proteins are located further away from the membrane in the cytosolic faces of the PSDs, facing the actin cytoskeleton. The rationale of this organization may be related to important roles of these proteins as "exchange hubs" for the signaling proteins for their migration from the subcortical cytosol to the membrane. Read More

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February 2015

DYNLL2 dynein light chain binds to an extended linear motif of myosin 5a tail that has structural plasticity.

Biochemistry 2014 Nov 5;53(45):7107-22. Epub 2014 Nov 5.

Laboratory of Structural Chemistry and Biology, Institute of Chemistry, and ‡Department of Biochemistry, Eötvös Loránd University , Budapest, 1117 Hungary.

LC8 dynein light chains (DYNLL) are conserved homodimeric eukaryotic hub proteins that participate in diverse cellular processes. Among the binding partners of DYNLL2, myosin 5a (myo5a) is a motor protein involved in cargo transport. Here we provide a profound characterization of the DYNLL2 binding motif of myo5a in free and DYNLL2-bound form by using nuclear magnetic resonance spectroscopy, X-ray crystallography, and molecular dynamics simulations. Read More

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November 2014

Polybivalency and disordered proteins in ordering macromolecular assemblies.

Semin Cell Dev Biol 2015 Jan 27;37:20-5. Epub 2014 Sep 27.

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

Intrinsically disordered proteins (IDPs) are prevalent in macromolecular assemblies and are thought to mediate protein recognition in complex regulatory processes and signaling pathways. The formation of a polybivalent scaffold is a key process by which IDPs drive early steps in macromolecular assemblies. Three intrinsically disordered proteins, IC, Swallow and Nup159, are core components, respectively, of cytoplasmic dynein, bicoid mRNA localization apparatus, and nuclear pore complexes. Read More

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January 2015

The mechanism of dynein light chain LC8-mediated oligomerization of the Ana2 centriole duplication factor.

J Biol Chem 2014 Jul 11;289(30):20727-39. Epub 2014 Jun 11.

From the Departments of Biology and

Centrioles play a key role in nucleating polarized microtubule networks. In actively dividing cells, centrioles establish the bipolar mitotic spindle and are essential for genomic stability. Drosophila anastral spindle-2 (Ana2) is a conserved centriole duplication factor. Read More

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NMR Characterization of Self-Association Domains Promoted by Interactions with LC8 Hub Protein.

Comput Struct Biotechnol J 2014 25;9:e201402003. Epub 2014 Feb 25.

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

Most proteins in interaction networks have a small number of partners, while a few, called hubs, participate in a large number of interactions and play a central role in cell homeostasis. One highly conserved hub is a protein called LC8 that was originally identified as an essential component of the multi-subunit complex dynein but later shown to be also critical in multiple protein complexes in diverse systems. What is intriguing about this hub protein is that it does not passively bind its various partners but emerging evidence suggests that LC8 acts as a dimerization engine that promotes self-association and/or higher order organization of its primarily disordered monomeric partners. Read More

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