Unraveling the structure and dynamics of the human DNAJB6b chaperone by NMR reveals insights into Hsp40-mediated proteostasis.

Abstract:

:J-domain chaperones are involved in the efficient handover of misfolded/partially folded proteins to Hsp70 but also function independently to protect against cell death. Due to their high flexibility, the mechanism by which they regulate the Hsp70 cycle and how specific substrate recognition is performed remains unknown. Here we focus on DNAJB6b, which has been implicated in various human diseases and represents a key player in protection against neurodegeneration and protein aggregation. Using a variant that exists mainly in a monomeric form, we report the solution structure of an Hsp40 containing not only the J and C-terminal substrate binding (CTD) domains but also the functionally important linkers. The structure reveals a highly dynamic protein in which part of the linker region masks the Hsp70 binding site. Transient interdomain interactions via regions crucial for Hsp70 binding create a closed, autoinhibited state and help retain the monomeric form of the protein. Detailed NMR analysis shows that the CTD (but not the J domain) self-associates to form an oligomer comprising ∼35 monomeric units, revealing an intricate balance between intramolecular and intermolecular interactions. The results shed light on the mechanism of autoregulation of the Hsp70 cycle via conserved parts of the linker region and reveal the mechanism of DNAJB6b oligomerization and potentially antiaggregation.

authors

Karamanos TK,Tugarinov V,Clore GM

doi

10.1073/pnas.1914999116

subject

Has Abstract

pub_date

2019-10-22 00:00:00

pages

21529-21538

issue

43

eissn

0027-8424

issn

1091-6490

pii

1914999116

journal_volume

116

pub_type

杂志文章
  • The LIM-domain binding protein Ldb1 and its partner LMO2 act as negative regulators of erythroid differentiation.

    abstract::The nuclear LIM domain protein LMO2, a T cell oncoprotein, is essential for embryonic erythropoiesis. LIM-only proteins are presumed to act primarily through protein-protein interactions. We, and others, have identified a widely expressed protein, Ldb1, whose C-terminal 76-residues are sufficient to mediate interactio...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.25.13707

    authors: Visvader JE,Mao X,Fujiwara Y,Hahm K,Orkin SH

    更新日期:1997-12-09 00:00:00

  • Scd1 controls de novo beige fat biogenesis through succinate-dependent regulation of mitochondrial complex II.

    abstract::Preadipocytes can give rise to either white adipocytes or beige adipocytes. Owing to their distinct abilities in nutrient storage and energy expenditure, strategies that specifically promote "beiging" of adipocytes hold great promise for counterbalancing obesity and metabolic diseases. Yet, factors dictating the diffe...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1914553117

    authors: Liu K,Lin L,Li Q,Xue Y,Zheng F,Wang G,Zheng C,Du L,Hu M,Huang Y,Shao C,Kong X,Melino G,Shi Y,Wang Y

    更新日期:2020-02-04 00:00:00

  • Heritable, population-wide damage to cells as the driving force of neoplastic transformation.

    abstract::Prolonged incubation of NIH 3T3 cells under the growth constraint of confluence results in the death of some cells in a manner suggestive of apoptosis. Successive rounds of prolonged incubation at confluence of the surviving cells produce increasing neoplastic transformation in the form of increments in saturation den...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.11.4843

    authors: Rubin H,Yao A,Chow M

    更新日期:1995-05-23 00:00:00

  • Recombinant human insulin-like growth factor I exerts a trophic action and confers glutamate sensitivity on glutamate-resistant cerebellar granule cells.

    abstract::Cerebellar granule cells grown in the presence of a serum complex differentiate but are resistant to the lethal action of excitatory amino acids. When these cells are grown also in the presence of insulin-like growth factor I (IGF-I) they become fully susceptible to the toxic, lethal action of glutamate. The glutamate...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.18.8752

    authors: Calissano P,Ciotti MT,Battistini L,Zona C,Angelini A,Merlo D,Mercanti D

    更新日期:1993-09-15 00:00:00

  • Reversal of DNA alkylation damage by two human dioxygenases.

    abstract::The Escherichia coli AlkB protein protects against the cytotoxicity of methylating agents by repair of the DNA lesions 1-methyladenine and 3-methylcytosine, which are generated in single-stranded stretches of DNA. AlkB is an alpha-ketoglutarate- and Fe(II)-dependent dioxygenase that oxidizes the relevant methyl groups...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.262589799

    authors: Duncan T,Trewick SC,Koivisto P,Bates PA,Lindahl T,Sedgwick B

    更新日期:2002-12-24 00:00:00

  • Dielectric constant of atomic fluids with variable polarizability.

    abstract::The Clausius-Mossotti function for the dielectric constant is expanded in terms of single atom and pair polarizabilities, leading to contributions that depend on both the trace and the anisotropy of the pair-polarizability tensor. The short-range contribution of the anisotropic part to the pair polarizabilities has pr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.77.6.3098

    authors: Alder BJ,Beers JC,Strauss HL,Weis JJ

    更新日期:1980-06-01 00:00:00

  • Nuclear magnetic resonance imaging and spectroscopy of human brain function.

    abstract::The techniques of in vivo magnetic resonance (MR) imaging and spectroscopy have been established over the past two decades. Recent applications of these methods to study human brain function have become a rapidly growing area of research. The development of methods using standard MR contrast agents within the cerebral...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.90.8.3127

    authors: Shulman RG,Blamire AM,Rothman DL,McCarthy G

    更新日期:1993-04-15 00:00:00

  • Highly enantioselective alkyne additions to aldehydes in the presence of 1,1'-bi-2-naphthol and hexamethylphosphoramide.

    abstract::It is found that the addition of hexamethylphosphoramide to the solution of an alkyne, Et(2)Zn, and (S)-1,1'-bi-2-naphthol in methylene chloride allows the generation of an alkynylzinc at room temperature and shows highly enantioselective additions to aldehydes. The mild condition for the formation of the alkynylzinc ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0307136101

    authors: Gao G,Xie RG,Pu L

    更新日期:2004-04-13 00:00:00

  • Modification of host dendritic cells by microchimerism-derived extracellular vesicles generates split tolerance.

    abstract::Maternal microchimerism (MMc) has been associated with development of allospecific transplant tolerance, antitumor immunity, and cross-generational reproductive fitness, but its mode of action is unknown. We found in a murine model that MMc caused exposure to the noninherited maternal antigens in all offspring, but in...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1618364114

    authors: Bracamonte-Baran W,Florentin J,Zhou Y,Jankowska-Gan E,Haynes WJ,Zhong W,Brennan TV,Dutta P,Claas FH,van Rood JJ,Burlingham WJ

    更新日期:2017-01-31 00:00:00

  • Site-specific recombinase and integrase activities of a conjugative relaxase in recipient cells.

    abstract::Conjugative relaxases are the proteins that initiate bacterial conjugation by a site-specific cleavage of the transferred DNA strand. In vitro, they show strand-transferase activity on single-stranded DNA, which suggests they may also be responsible for recircularization of the transferred DNA. In this work, we show t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0506081102

    authors: Draper O,César CE,Machón C,de la Cruz F,Llosa M

    更新日期:2005-11-08 00:00:00

  • Lazaroids improve the survival of grafted rat embryonic dopamine neurons.

    abstract::In rodent models of Parkinson disease in which transplants of dissociated rodent and human embryonic mesencephalic tissue, rich in dopamine neurons, have been studied, only 5-20% of the dopamine neurons survive the implantation procedure. We have investigated the effects of inhibiting free radical generation with two ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.26.12408

    authors: Nakao N,Frodl EM,Duan WM,Widner H,Brundin P

    更新日期:1994-12-20 00:00:00

  • beta2-chimaerin is a novel target for diacylglycerol: binding properties and changes in subcellular localization mediated by ligand binding to its C1 domain.

    abstract::The members of the chimaerin family of Rac-GTPase-activating proteins possess a single C1 domain with high homology to those present in protein kinase C (PKC) isozymes. This domain in PKCs is involved in phorbol ester and diacylglycerol (DAG) binding. We previously have demonstrated that one of the chimaerin isoforms,...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.21.11854

    authors: Caloca MJ,Garcia-Bermejo ML,Blumberg PM,Lewin NE,Kremmer E,Mischak H,Wang S,Nacro K,Bienfait B,Marquez VE,Kazanietz MG

    更新日期:1999-10-12 00:00:00

  • In vivo expression of the lacY gene in two segments leads to functional lac permease.

    abstract::The lacY gene of Escherichia coli was cut into two approximately equal-size fragments with Afl II and subcloned individually or together under separate lac operator/promoters in plasmid pT7-5. Under these conditions, lac permease is expressed in two portions: (i) the N-terminal portion (the N terminus, the first six p...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.11.4325

    authors: Bibi E,Kaback HR

    更新日期:1990-06-01 00:00:00

  • Mechanism of penicillin action: penicillin and substrate bind covalently to the same active site serine in two bacterial D-alanine carboxypeptidases.

    abstract::It has been hypothesized that penicillin acts as a structural analog of the acyl-D-alanyl-D-alanine terminus of nascent bacterial cell wall and that it consequently binds to and acylates the active site of the enzyme(s) that crosslinks the cell wall to form an inactive penicilloyl enzyme [Tipper, D.J. & Strominger, J....

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.6.2730

    authors: Yocum RR,Waxman DJ,Rasmussen JR,Strominger JL

    更新日期:1979-06-01 00:00:00

  • One SUMO is sufficient to silence the dimeric potassium channel K2P1.

    abstract::Small ubiquitin modifier 1 (SUMO1) is shown to regulate K2P1 background channels in the plasma membrane (PM) of live mammalian cells. Confocal microscopy reveals native SUMO1, SAE1, and Ubc9 (the enzymes that activate and conjugate SUMO1) at PM where SUMO1 and expressed human K2P1 are demonstrated to colocalize. Silen...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1004712107

    authors: Plant LD,Dementieva IS,Kollewe A,Olikara S,Marks JD,Goldstein SA

    更新日期:2010-06-08 00:00:00

  • Identification and primary sequence of an unspliced human urokinase poly(A)+ RNA.

    abstract::Human urokinase cDNA clones have been identified from a cDNA library prepared from total RNA of human fibroblasts transformed by simian virus 40 [Okayama, H. & Berg, P. (1983) Mol. Cell. Biol. 3, 280-289]. Synthetic oligonucleotides, corresponding to urokinase protein sequence, were used as probes. The cloned cDNA cov...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.15.4727

    authors: Verde P,Stoppelli MP,Galeffi P,Di Nocera P,Blasi F

    更新日期:1984-08-01 00:00:00

  • Aging reduces neural specialization in ventral visual cortex.

    abstract::The present study investigated whether neural structures become less functionally differentiated and specialized with age. We studied ventral visual cortex, an area of the brain that responds selectively to visual categories (faces, places, and words) in young adults, and that shows little atrophy with age. Functional...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0405148101

    authors: Park DC,Polk TA,Park R,Minear M,Savage A,Smith MR

    更新日期:2004-08-31 00:00:00

  • Identification and radiochemical purification of the recA protein of Escherichia coli K-12.

    abstract::The product of the recA gene of E. coli has been identified by labeling proteins synthesized in UV-treated cells after infection with specialized transducing phages carrying the recA gene. Following infection of UV-treated cells by lambda precA, which carries the recA+ gene, a major protein with a molecular weight of ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.73.11.3979

    authors: McEntee K,Hesse JE,Epstein W

    更新日期:1976-11-01 00:00:00

  • Protein-solvent preferential interactions, protein hydration, and the modulation of biochemical reactions by solvent components.

    abstract::Solvent additives (cosolvents, osmolytes) modulate biochemical reactions if, during the course of the reaction, there is a change in preferential interactions of solvent components with the reacting system. Preferential interactions can be expressed in terms of preferential binding of the cosolvent or its preferential...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.122225399

    authors: Timasheff SN

    更新日期:2002-07-23 00:00:00

  • Covalent crosslinking of tRNA1Val to 16S RNA at the ribosomal P site: identification of crosslinked residues.

    abstract::N-Acetylvalyl-tRNA1Val (AcVal-tRNA1Val) was bound to the P site of uniformly 32P-labeled 70S ribosomes from Escherichia coli and crosslinked to 16S RNA in the 30S ribosomal subunit by irradiation with light of 300-400 nm. To identify the crosslinked nucleotide in 16S RNA. AcVal-tRNA1Val-16S [32P]RNA was digested compl...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.18.5450

    authors: Prince JB,Taylor BH,Thurlow DL,Ofengand J,Zimmermann RA

    更新日期:1982-09-01 00:00:00

  • Ribosome clearance by FusB-type proteins mediates resistance to the antibiotic fusidic acid.

    abstract::Resistance to the antibiotic fusidic acid (FA) in the human pathogen Staphylococcus aureus usually results from expression of FusB-type proteins (FusB or FusC). These proteins bind to elongation factor G (EF-G), the target of FA, and rescue translation from FA-mediated inhibition by an unknown mechanism. Here we show ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1117275109

    authors: Cox G,Thompson GS,Jenkins HT,Peske F,Savelsbergh A,Rodnina MV,Wintermeyer W,Homans SW,Edwards TA,O'Neill AJ

    更新日期:2012-02-07 00:00:00

  • The amino acid sensor GCN2 inhibits inflammatory responses to apoptotic cells promoting tolerance and suppressing systemic autoimmunity.

    abstract::Efficient apoptotic cell clearance and induction of immunologic tolerance is a critical mechanism preventing autoimmunity and associated pathology. Our laboratory has reported that apoptotic cells induce tolerance by a mechanism dependent on the tryptophan catabolizing enzyme indoleamine 2,3 dioxygenase 1 (IDO1) in sp...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1504276112

    authors: Ravishankar B,Liu H,Shinde R,Chaudhary K,Xiao W,Bradley J,Koritzinsky M,Madaio MP,McGaha TL

    更新日期:2015-08-25 00:00:00

  • Length suppression in histone messenger RNA 3'-end maturation: processing defects of insertion mutant premessenger RNAs can be compensated by insertions into the U7 small nuclear RNA.

    abstract::Efficient 3'-end processing of cell cycle-regulated mammalian histone premessenger RNAs (pre-mRNAs) requires an upstream stem-loop and a histone downstream element (HDE) that base pairs with the U7 small ribonucleoprotein. Insertions between these elements have two effects: the site of cleavage moves in concert with t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.25.14659

    authors: Scharl EC,Steitz JA

    更新日期:1996-12-10 00:00:00

  • Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy.

    abstract::The Parkinson's disease (PD) substantia nigra is characterized by the presence of Lewy bodies containing fibrillar alpha-synuclein. Early-onset PD has been linked to two point mutations in the gene that encodes alpha-synuclein, suggesting that disease may arise from accelerated fibrillization. However, the identity of...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.97.2.571

    authors: Conway KA,Lee SJ,Rochet JC,Ding TT,Williamson RE,Lansbury PT Jr

    更新日期:2000-01-18 00:00:00

  • Tumor promoter TPA activates Wnt/β-catenin signaling in a casein kinase 1-dependent manner.

    abstract::The tumor promoter 12-O-tetra-decanoylphorbol-13-acetate (TPA) has been defined by its ability to promote tumorigenesis on carcinogen-initiated mouse skin. Activation of Wnt/β-catenin signaling has a decisive role in mouse skin carcinogenesis, but it remains unclear how TPA activates Wnt/β-catenin signaling in mouse s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1802422115

    authors: Su Z,Song J,Wang Z,Zhou L,Xia Y,Yu S,Sun Q,Liu SS,Zhao L,Li S,Wei L,Carson DA,Lu D

    更新日期:2018-08-07 00:00:00

  • Genotypic analysis of N-ethyl-N-nitrosourea-induced mutations by Taq I restriction fragment length polymorphism/polymerase chain reaction in the c-H-ras1 gene.

    abstract::In genotypic mutation analysis DNA sequence changes are determined without the in vivo or in vitro selection of phenotypically altered cells. We have studied the induction of base-pair changes by N-ethyl-N-nitrosourea in Taq I endonuclease recognition site 2508-2511 (TCGA) of the c-H-ras1 gene in human fibroblasts by ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.12.5331

    authors: Chiocca SM,Sandy MS,Cerutti PA

    更新日期:1992-06-15 00:00:00

  • Catalytic asymmetric addition of diphenylzinc to cyclic alpha,beta-unsaturated ketones.

    abstract::We have examined the use of our bis(sulfonamide) diol ligand (1) in the asymmetric addition of phenyl groups to cyclic alpha,beta-unsaturated ketones. Good to excellent enantioselectivities have been obtained with cyclic enones bearing alkyl substituents in the 2 position (71-97% enantiomeric excess). Furthermore, exc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0307119101

    authors: Li H,García C,Walsh PJ

    更新日期:2004-04-13 00:00:00

  • Success or failure of vaccination for HPV16-positive vulvar lesions correlates with kinetics and phenotype of induced T-cell responses.

    abstract::One half of a group of 20 patients with human papillomavirus type 16 (HPV16)-induced vulvar intraepithelial neoplasia grade 3 displayed a complete regression (CR) after therapeutic vaccination with HPV16 E6/E7 synthetic long peptides. Patients with relatively larger lesions generally did not display a CR. To investiga...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1006500107

    authors: Welters MJ,Kenter GG,de Vos van Steenwijk PJ,Löwik MJ,Berends-van der Meer DM,Essahsah F,Stynenbosch LF,Vloon AP,Ramwadhdoebe TH,Piersma SJ,van der Hulst JM,Valentijn AR,Fathers LM,Drijfhout JW,Franken KL,Oostendorp J,Fle

    更新日期:2010-06-29 00:00:00

  • Structural studies of isolated native thick filaments from rabbit psoas muscle with AMP deaminase decoration.

    abstract::AMP deaminase (adenylate deaminase; AMP aminohydrolase, EC 3.5.4.6), a large flat tetrameric enzyme found in skeletal muscle, binds strongly and specifically to the subfragment-2 region of rabbit skeletal muscle myosin. This allows its use as a structural probe in myosin and myosin rod aggregation studies. When mixed ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.20.6205

    authors: Koretz JF

    更新日期:1982-10-01 00:00:00

  • Pattern of mutation in the genome of influenza A virus on adaptation to increased virulence in the mouse lung: identification of functional themes.

    abstract::The genetic basis for virulence in influenza virus is largely unknown. To explore the mutational basis for increased virulence in the lung, the H3N2 prototype clinical isolate, A/HK/1/68, was adapted to the mouse. Genomic sequencing provided the first demonstration, to our knowledge, that a group of 11 mutations can c...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.111165798

    authors: Brown EG,Liu H,Kit LC,Baird S,Nesrallah M

    更新日期:2001-06-05 00:00:00