25 results match your criteria lc8 bound

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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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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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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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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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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

Arl3 and LC8 regulate dissociation of dynactin from dynein.

Nat Commun 2014 Oct 24;5:5295. Epub 2014 Oct 24.

Department of Genetic Disease Research, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno, Osaka 545-8585, Japan.

Cytoplasmic dynein acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. However, the regulatory mechanism underlying release of dynactin bound cargoes from dynein motor remains largely unknown. Here we report that ADP-ribosylation factor-like 3 (Arl3) and dynein light chain LC8 induce dissociation of dynactin from dynein. Read More

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October 2014

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 versatile molecular complex component LC8 promotes several distinct steps of flagellar assembly.

J Cell Biol 2012 Jul 2;198(1):115-26. Epub 2012 Jul 2.

Department of Biological Sciences, Marquette University, Milwaukee, WI 53201, USA.

LC8 is present in various molecular complexes. However, its role in these complexes remains unclear. We discovered that although LC8 is a subunit of the radial spoke (RS) complex in Chlamydomonas flagella, it was undetectable in the RS precursor that is converted into the mature RS at the tip of elongating axonemes. Read More

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ATM substrate Chk2-interacting Zn2+ finger (ASCIZ) Is a bi-functional transcriptional activator and feedback sensor in the regulation of dynein light chain (DYNLL1) expression.

J Biol Chem 2012 Jan 13;287(5):3156-64. Epub 2011 Dec 13.

St. Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia.

The highly conserved DYNLL1 (LC8) protein was originally discovered as a light chain of the dynein motor complex, but is increasingly emerging as a sequence-specific regulator of protein dimerization with hundreds of targets and wide-ranging cellular functions. Despite its important roles, DYNLL1's own regulation remains poorly understood. Here we identify ASCIZ (ATMIN/ZNF822), an essential Zn(2+) finger protein with dual roles in the DNA base damage response and as a developmental transcription factor, as a conserved regulator of Dynll1 gene expression. Read More

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January 2012

Myosin Va plays a key role in nitrergic neurotransmission by transporting nNOSα to enteric varicosity membrane.

Am J Physiol Gastrointest Liver Physiol 2011 Sep 16;301(3):G498-507. Epub 2011 Jun 16.

Center for Swallowing & Motility Disorders, VA Boston HealthCare System and Harvard Medical School, Boston, Massachusetts, USA.

Nitrergic neurotransmission at the smooth muscle neuromuscular junctions requires nitric oxide (NO) release that is dependent on the transport and docking of neuronal NO synthase (nNOS) α to the membrane of nerve terminals. However, the mechanism of translocation of nNOSα in actin-rich varicosities is unknown. We report here that the processive motor protein myosin Va is necessary for nitrergic neurotransmission. Read More

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September 2011

Conformational dynamics promote binding diversity of dynein light chain LC8.

Biophys Chem 2011 Nov 6;159(1):41-7. Epub 2011 May 6.

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

A highly conserved and ubiquitous protein known as LC8 binds over twenty different partners, characteristic of a molecular hub (Barbar, 2008 Biochemistry, 47, 503-508). Structural studies of LC8 complexes with binding partners having diverse recognition sequences show that the same binding groove of LC8 accommodates the various binding motifs. Here we use thermodynamics and dynamics measurements of LC8 complexes to group LC8 binding partners in two categories: those whose binding is enthalpically driven and those that are entropically favored. Read More

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November 2011

Light chain-dependent self-association of dynein intermediate chain.

J Biol Chem 2011 Jan 25;286(2):1556-66. Epub 2010 Oct 25.

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

Dynein light chains are bivalent dimers that bind two copies of dynein intermediate chain IC to form a cargo attachment subcomplex. The interaction of light chain LC8 with the natively disordered N-terminal domain of IC induces helix formation at distant IC sites in or near a region predicted to form a coiled-coil. This fostered the hypothesis that LC8 binding promotes IC self-association to form a coiled-coil or other interchain helical structure. Read More

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January 2011

Structural, thermodynamic, and kinetic effects of a phosphomimetic mutation in dynein light chain LC8.

Biochemistry 2009 Dec;48(48):11381-9

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

Dynein light chain LC8 is a small, dimeric, very highly conserved globular protein first identified as an integral part of the dynein and myosin molecular motors but now recognized as a dimerization hub with wider significance. Phosphorylation at Ser88 is thought to be involved in regulating LC8 in the apoptotic pathway. The phosphomimetic Ser88Glu mutation weakens dimerization of LC8 and thus its overall ligand-binding affinity, because only the dimer binds ligands. Read More

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December 2009

Multivalency in the assembly of intrinsically disordered Dynein intermediate chain.

J Biol Chem 2009 Nov 16;284(48):33115-21. Epub 2009 Sep 16.

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

Dynein light chains are thought to increase binding efficiency of dynein intermediate chain to both dynein heavy chain and dynactin, but their exact role is not clear. Isothermal titration calorimetry and x-ray crystallography reported herein indicate that multivalency effects underlie efficient dynein assembly and regulation. For a ternary complex of a 60-amino acid segment of dynein intermediate chain (IC) bound to two homodimeric dynein light chains Tctex1 and LC8, there is a 50-fold affinity enhancement for the second light chain binding. Read More

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November 2009

PIN/LC8 is associated with cytosolic but not membrane-bound nNOS in the nitrergic varicosities of mice gut: implications for nitrergic neurotransmission.

Am J Physiol Gastrointest Liver Physiol 2008 Sep 17;295(3):G442-51. Epub 2008 Jul 17.

Center for Swallowing and Motility Disorders, Veterans Affairs Boston Healthcare System and Harvard Medical Center, Boston, MA, USA.

This investigation demonstrates the presence and binding of the protein LC8 (described as "protein inhibitor of nNOS" or PIN in some reports) to different components of neuronal nitric oxide synthase (nNOS) in nitrergic varicosities of mice gut. Whole varicosity extracts showed three (320-, 250-, and 155-kDa) nNOS bands with anti-nNOS(1422-1433) antibody and a 10-kDa band with anti-LC8 antibody. The LC8 immunoprecipitate (IP) showed three nNOS bands, suggesting that LC8 was bound with all three forms of nNOS but dissociated from them during SDS-PAGE. Read More

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September 2008

Structure and dynamics of LC8 complexes with KXTQT-motif peptides: swallow and dynein intermediate chain compete for a common site.

J Mol Biol 2007 Aug 24;371(2):457-68. Epub 2007 May 24.

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

The dynein light chain LC8 is an integral subunit of the cytoplasmic dynein motor complex that binds directly to and promotes assembly of the dynein intermediate chain (IC). LC8 interacts also with a variety of putative dynein cargo molecules such as Bim, a proapoptotic Bcl2 family protein, which have the KXTQT recognition sequence and neuronal nitric oxide synthase (nNOS), which has the GIQVD fingerprint but shares the same binding grooves at the LC8 dimer interface. The work reported here investigates the interaction of LC8 with IC and a putative cargo, Swallow, which share the KXTQT recognition sequence, and addresses the apparent paradox of how LC8, as part of dynein, mediates binding to cargo. Read More

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Evaluation of an LC8-binding peptide for the attachment of artificial cargo to dynein.

Mol Pharm 2007 Jan-Feb;4(1):119-28

Department of Bioengineering, University of Washington, Seattle, Washington 98195, USA.

The limited cytoplasmic mobility of nonviral gene carriers is likely to contribute to their low transfection efficiency. This limitation could be overcome by mimicking the viral strategy of recruiting the dynein motor complex for efficient transport toward the host cell nucleus. A promising approach for attaching artificial cargo to dynein is through an adaptor peptide that binds the 8 kDa light chain (LC8) found in the cargo-binding region of the dynein complex. Read More

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Constitutive association of the proapoptotic protein Bim with Bcl-2-related proteins on mitochondria in T cells.

Proc Natl Acad Sci U S A 2004 May 10;101(20):7681-6. Epub 2004 May 10.

Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver, CO 80262, USA.

Apoptosis in activated T cells in vivo requires the proapoptotic Bcl-2 family member Bim. We show here that, despite its ability to bind LC8, a component of the microtubule dynein motor complex, most of the Bim in both healthy and apoptotic T cells is associated with mitochondria, not microtubules. In healthy resting T cells Bim is bound to the antiapoptotic proteins Bcl-2 and Bcl-x(L). Read More

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Interactions of LC8 with N-terminal segments of the intermediate chain of cytoplasmic dynein.

ScientificWorldJournal 2003 Aug 2;3:647-54. Epub 2003 Aug 2.

Department of Chemistry and Biochemistry, Ohio University, Athens, Ohio 45701, USA.

LC8, a highly conserved 10-kDa light chain, and IC74, a 74-kDa intermediate chain, are presumed to promote the assembly of the cytoplasmic dynein motor protein complex and to be engaged in the controlled binding and release of cargo. The interactions of LC8 from Drosophila melanogaster with constructs of IC74 were characterized in vitro by affinity methods, limited proteolysis, and circular dichroism spectroscopy. Previously, we have performed limited proteolysis on the N-terminal domain of IC74, IC(1-289), when free and when bound to dynein light chains LC8 and Tctex-1. Read More

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Gephyrin interacts with Dynein light chains 1 and 2, components of motor protein complexes.

J Neurosci 2002 Jul;22(13):5393-402

Max-Planck-Institute for Brain Research, Department of Neurochemistry, D-60528 Frankfurt/Main, Germany.

The clustering of glycine receptors and major subtypes of GABA(A) receptors at inhibitory synapses is mediated by the tubulin-binding protein gephyrin. In an attempt to identify additional components of inhibitory postsynaptic specializations, we performed a yeast two-hybrid screen using gephyrin as bait. Multiple positive clones encoded either the dynein light chain-1 (Dlc-1), also known as dynein LC8 and protein inhibitor of neuronal nitric oxide synthase, or its homolog Dlc-2. Read More

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Molecular basis for the interaction between rabies virus phosphoprotein P and the dynein light chain LC8: dissociation of dynein-binding properties and transcriptional functionality of P.

J Gen Virol 2001 Nov;82(Pt 11):2691-2696

Laboratoire de Génétique des Virus, CNRS, 91198 Gif sur Yvette, France1.

The lyssavirus phosphoprotein P is a co-factor of the viral RNA polymerase and plays a central role in virus transcription and replication. It has been shown previously that P interacts with the dynein light chain LC8, which is involved in minus end-directed movement of organelles along microtubules. Co-immunoprecipitation experiments and the two-hybrid system were used to map the LC8-binding site to the sequence (139)RSSEDKSTQTTGR(151). Read More

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November 2001

Structure of the PIN/LC8 dimer with a bound peptide.

Nat Struct Biol 1999 Aug;6(8):735-40

Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853-1301, USA.

The structure of the protein known both as neuronal nitric oxide synthase inhibitory protein, PIN (protein inhibitor of nNOS), and also as the 8 kDa dynein light chain (LC8) has been solved by X-ray diffraction. Two PIN/LC8 monomers related by a two-fold axis form a rectangular dimer. Two pairs of alpha-helices cover opposite faces, and each pair of helices packs against a beta-sheet with five antiparallel beta-strands. Read More

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The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex.

Mol Cell 1999 Mar;3(3):287-96

Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.

Bcl-2 family members that have only a single Bcl-2 homology domain, BH3, are potent inducers of apoptosis, and some appear to play a critical role in developmentally programmed cell death. We examined the regulation of the proapoptotic activity of the BH3-only protein Bim. In healthy cells, most Bim molecules were bound to LC8 cytoplasmic dynein light chain and thereby sequestered to the microtubule-associated dynein motor complex. Read More

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