Correlation between conformational and binding properties of nebulin repeats.


:Nebulin, a large protein (600 to 800 kDa) located in the thin filament of striated vertebrate muscle, is assumed to bind and stabilise F-actin. Complete sequence determination of human nebulin has only recently been accomplished showing a uniform modular structure along the whole length of the molecule. Up to 97% of the sequence is assembled from repeats of a sequence motif 35 amino acid residues long. This architecture suggests that a structural and functional understanding of such a large molecule may be possible by characterising single repeats and reconstructing from them the behaviour of the whole molecule. In the present study, we extend and generalise to the whole molecule previous work carried out on single repeats from a limited region of nebulin. Knowledge of the complete sequence allowed extensive analysis of the single repeats revealing a progressive N to C-terminal divergence that is mirrored by an increase of the alpha-helix propensity. A number of synthetic peptides spanning the sequences of selected repeats were obtained and their conformational and binding properties studied in detail. All the peptides showed a tendency to fold as transient helices in aqueous solution with helix content as observed by CD and NMR studies in excellent agreement with predictions. A higher helical tendency of repeats near the C terminus was observed. Analysis of the influence of charged media as well as trifluoroethanol on the folding of single repeats strongly suggested that the mechanism by which the nebulin alpha-helix is stabilised is mostly electrostatic. Peptides with higher helical content also showed a higher binding affinity to F-actin. Considerably varying effects were observed for the peptides on F-actin viscosity and polymerisation. We discuss the divergence in sequence and helical tendency and its correlation to the functional data with regard to their significance for the assembly of the thin filament during myogenesis.


J Mol Biol


Pfuhl M,Winder SJ,Castiglione Morelli MA,Labeit S,Pastore A




Has Abstract


1996-03-29 00:00:00














  • Crystal structure of desulforedoxin from Desulfovibrio gigas determined at 1.8 A resolution: a novel non-heme iron protein structure.

    abstract::The crystal structure of desulforedoxin from Desulfovibrio gigas, a new homo-dimeric (2 x 36 amino acids) non-heme iron protein, has been solved by the SIRAS method using the indium-substituted protein as the single derivative. The structure was refined to a crystallographic R-factor of 16.9% at 1.8 A resolution. Nati...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Archer M,Huber R,Tavares P,Moura I,Moura JJ,Carrondo MA,Sieker LC,LeGall J,Romão MJ

    更新日期:1995-09-01 00:00:00

  • Crystallization and preliminary crystallographic studies of the decadeoxyoligonucleotide d(CpGpTpApCpGpTpApCpG).

    abstract::Crystals of the self-complementary decadeoxyoligonucleotide d(CpGpTpApCpGpTpApCpG) have been grown from a solution containing [Co(NH3)6]Cl3 and spermine. The amber-colored crystals are hexagonal and belong to the space group P6(5) (or P6(1] with unit cell parameters a = 17.93 A, c = 43.41 A. Precession photography and...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Brennan RG,Sundaralingam M

    更新日期:1985-02-20 00:00:00

  • Prohead and DNA-gp3-dependent ATPase activity of the DNA packaging protein gp16 of bacteriophage phi 29.

    abstract::The ATPase activity of the DNA packaging protein gp16 (gene product 16) of bacteriophage phi 29 was studied in the completely defined in-vitro assembly system. ATP was hydrolyzed to ADP and Pi in the packaging reaction that included purified proheads, DNA-gp3 and gp16. Approximately one molecule of ATP was used in the...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Guo P,Peterson C,Anderson D

    更新日期:1987-09-20 00:00:00

  • Structural evidence of a passive base-flipping mechanism for AGT, an unusual GT-B glycosyltransferase.

    abstract::The Escherichia coli T4 bacteriophage uses two glycosyltransferases to glucosylate and thus protect its DNA: the retaining alpha-glucosyltransferase (AGT) and the inverting beta-glucosyltransferase (BGT). They glucosylate 5-hydroxymethyl cytosine (5-HMC) bases of duplex DNA using UDP-glucose as the sugar donor to form...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Larivière L,Sommer N,Moréra S

    更新日期:2005-09-09 00:00:00

  • Cold-adaptation in sea-water-borne signal proteins: sequence and NMR structure of the pheromone En-6 from the Antarctic ciliate Euplotes nobilii.

    abstract::Ciliates of Euplotes species constitutively secrete pleiotropic protein pheromones, which are capable to function as prototypic autocrine growth factors as well as paracrine inducers of mating processes. This paper reports the amino acid sequence and the NMR structure of the pheromone En-6 isolated from the antarctic ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Pedrini B,Placzek WJ,Koculi E,Alimenti C,LaTerza A,Luporini P,Wüthrich K

    更新日期:2007-09-14 00:00:00

  • Full-length rat alpha and beta cardiac myosin heavy chain sequences. Comparisons suggest a molecular basis for functional differences.

    abstract::The two cardiac myosin heavy chain isoforms, alpha and beta, differ functionally, alpha Myosin exhibits higher actin-activated ATPase than does beta myosin, and hearts expressing alpha myosin exhibit increased contractility relative to hearts expressing beta myosin. To understand the molecular basis for this functiona...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: McNally EM,Kraft R,Bravo-Zehnder M,Taylor DA,Leinwand LA

    更新日期:1989-12-05 00:00:00

  • The Spliceosomal Protein SF3B5 is a Novel Component of Drosophila SAGA that Functions in Gene Expression Independent of Splicing.

    abstract::The interaction between splicing factors and the transcriptional machinery provides an intriguing link between the coupled processes of transcription and splicing. Here, we show that the two components of the SF3B complex, SF3B3 and SF3B5, that form part of the U2 small nuclear ribonucleoprotein particle (snRNP) are a...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Stegeman R,Spreacker PJ,Swanson SK,Stephenson R,Florens L,Washburn MP,Weake VM

    更新日期:2016-09-11 00:00:00

  • Binding and Action of Amino Acid Analogs of Chloramphenicol upon the Bacterial Ribosome.

    abstract::Antibiotic chloramphenicol (CHL) binds with a moderate affinity at the peptidyl transferase center of the bacterial ribosome and inhibits peptide bond formation. As an approach for modifying and potentially improving properties of this inhibitor, we explored ribosome binding and inhibitory activity of a number of amin...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Tereshchenkov AG,Dobosz-Bartoszek M,Osterman IA,Marks J,Sergeeva VA,Kasatsky P,Komarova ES,Stavrianidi AN,Rodin IA,Konevega AL,Sergiev PV,Sumbatyan NV,Mankin AS,Bogdanov AA,Polikanov YS

    更新日期:2018-03-16 00:00:00

  • Solid-state NMR spectroscopy of the HIV gp41 membrane fusion protein supports intermolecular antiparallel β sheet fusion peptide structure in the final six-helix bundle state.

    abstract::The HIV gp41 protein catalyzes fusion between viral and target cell membranes. Although the ~20-residue N-terminal fusion peptide (FP) region is critical for fusion, the structure of this region is not well characterized in large gp41 constructs that model the gp41 state at different times during fusion. This paper de...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Sackett K,Nethercott MJ,Zheng Z,Weliky DP

    更新日期:2014-03-06 00:00:00

  • Structural and Functional Characterization of the BcsG Subunit of the Cellulose Synthase in Salmonella typhimurium.

    abstract::Many bacteria secrete cellulose, which forms the structural basis for bacterial multicellular aggregates, termed biofilms. The cellulose synthase complex of Salmonella typhimurium consists of the catalytic subunits BcsA and BcsB and several auxiliary subunits that are encoded by two divergently transcribed operons, bc...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Sun L,Vella P,Schnell R,Polyakova A,Bourenkov G,Li F,Cimdins A,Schneider TR,Lindqvist Y,Galperin MY,Schneider G,Römling U

    更新日期:2018-09-14 00:00:00

  • FOXO4 Transactivation Domain Interaction with Forkhead DNA Binding Domain and Effect on Selective DNA Recognition for Transcription Initiation.

    abstract::Forkhead box O4 (FOXO4) is a human transcription factor (TF) that participates in cell homeostasis. While the structure and DNA binding properties of the conserved forkhead domain (FHD) have been thoroughly investigated, how the transactivation domain (TAD) regulates the DNA binding properties of the protein remains e...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Kim J,Ahn D,Park CJ

    更新日期:2021-01-13 00:00:00

  • Thermal expansion of hen egg-white lysozyme. Comparison of the 1.9 A resolution structures of the tetragonal form of the enzyme at 100 K and 298 K.

    abstract::The average structural and dynamic properties of tetragonal hen egg-white lysozyme have been compared, in structures refined at 1.9 A resolution, using data collected at 100 K and 298 K. The molecule expands by 1.8% over this temperature range with the expansion occurring primarily in its small sub-atomic-sized spaces...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Young AC,Tilton RF,Dewan JC

    更新日期:1994-01-07 00:00:00

  • The FGFR D3 domain determines receptor selectivity for fibroblast growth factor 21.

    abstract::FGF21 is a member of a unique subfamily of fibroblast growth factors that function as endocrine hormones and regulate a variety of metabolic activities. Unlike paracrine FGFs, FGF21 does not bind heparin and requires βKlotho as a co-receptor to activate FGFR signaling. In the presence of βKlotho, FGF21 is able to acti...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Gupte J,Yang L,Wu X,Weiszmann J,Hecht R,Lemon B,Lindberg R,Wang Z,Li Y

    更新日期:2011-05-06 00:00:00

  • The complete nucleotide sequence of a plant root-inducing (Ri) plasmid indicates its chimeric structure and evolutionary relationship between tumor-inducing (Ti) and symbiotic (Sym) plasmids in Rhizobiaceae.

    abstract::The Ri (root-inducing) plasmid in Agrobacterium rhizogenes and Ti (tumor-inducing) plasmid in Agrobacterium tumefaciens have provided the fundamental basis for the construction of plant vectors and transgenic plants. Recently, the determination of the first complete nucleotide sequence of the Ti plasmid (pTi-SAKURA) h...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Moriguchi K,Maeda Y,Satou M,Hardayani NS,Kataoka M,Tanaka N,Yoshida K

    更新日期:2001-03-30 00:00:00

  • The structural basis of riboflavin binding to Schizosaccharomyces pombe 6,7-dimethyl-8-ribityllumazine synthase.

    abstract::Riboflavin is an essential cofactor in all organisms. Its direct biosynthetic precursor, 6,7-dimethyl-8-ribityllumazine, is synthesised by the enzyme 6,7-dimethyl-8-ribityllumazine synthase. Recently, we have found that the enzyme from Schizosaccharomyces pombe binds riboflavin, the final product of the pathway with a...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Gerhardt S,Haase I,Steinbacher S,Kaiser JT,Cushman M,Bacher A,Huber R,Fischer M

    更新日期:2002-05-17 00:00:00

  • Studies of the RNA degradosome-organizing domain of the Escherichia coli ribonuclease RNase E.

    abstract::The hydrolytic endoribonuclease RNase E, which is widely distributed in bacteria and plants, plays key roles in mRNA degradation and RNA processing in Escherichia coli. The enzymatic activity of RNase E is contained within the conserved amino-terminal half of the 118 kDa protein, and the carboxy-terminal half organize...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Callaghan AJ,Aurikko JP,Ilag LL,Günter Grossmann J,Chandran V,Kühnel K,Poljak L,Carpousis AJ,Robinson CV,Symmons MF,Luisi BF

    更新日期:2004-07-23 00:00:00

  • Interplay between hydrophobic cluster and loop propensity in beta-hairpin formation.

    abstract::Autonomously folding beta-hairpins have recently emerged as powerful tools for elucidating the origins of antiparallel beta-sheet folding preferences. Analysis of such model systems has suggested four potential sources of beta-sheet stability: (1) the conformational propensity of the loop segment that connects adjacen...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Espinosa JF,Muñoz V,Gellman SH

    更新日期:2001-02-23 00:00:00

  • Inverting enantioselectivity of Burkholderia cepacia KWI-56 lipase by combinatorial mutation and high-throughput screening using single-molecule PCR and in vitro expression.

    abstract::The enantioselectivity of lipase from Burkhorderia cepacia KWI-56 has been inverted using a novel in vitro technique for construction and screening of a protein library by single-molecule DNA amplification by PCR followed by in vitro coupled transcription/translation system termed single-molecule-PCR-linked in vitro e...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Koga Y,Kato K,Nakano H,Yamane T

    更新日期:2003-08-15 00:00:00

  • Crystal structure of the agrin-responsive immunoglobulin-like domains 1 and 2 of the receptor tyrosine kinase MuSK.

    abstract::Muscle-specific kinase (MuSK) is a receptor tyrosine kinase expressed exclusively in skeletal muscle, where it is required for formation of the neuromuscular junction. MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. Here, we report the crystal structure of the agrin-responsive first and seco...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Stiegler AL,Burden SJ,Hubbard SR

    更新日期:2006-12-01 00:00:00

  • The structure of the Sec13/31 COPII cage bound to Sec23.

    abstract::Structural studies have revealed some of the organizing principles and mechanisms involved in the assembly of the COPII coat including the location of the Sec23/24 adapter layer. Previous studies, however, were unable to unambiguously determine the positions of Sec23 and Sec24 in the coat. Here, we have determined a c...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Bhattacharya N,O Donnell J,Stagg SM

    更新日期:2012-07-20 00:00:00

  • Advances in Understanding Stimulus-Responsive Phase Behavior of Intrinsically Disordered Protein Polymers.

    abstract::Proteins and synthetic polymers can undergo phase transitions in response to changes to intensive solution parameters such as temperature, proton chemical potentials (pH), and hydrostatic pressure. For proteins and protein-based polymers, the information required for stimulus-responsive phase transitions is encoded in...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章,评审


    authors: Ruff KM,Roberts S,Chilkoti A,Pappu RV

    更新日期:2018-11-02 00:00:00

  • Common core structure of amyloid fibrils by synchrotron X-ray diffraction.

    abstract::Tissue deposition of normally soluble proteins as insoluble amyloid fibrils is associated with serious diseases including the systemic amyloidoses, maturity onset diabetes, Alzheimer's disease and transmissible spongiform encephalopathy. Although the precursor proteins in different diseases do not share sequence homol...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Sunde M,Serpell LC,Bartlam M,Fraser PE,Pepys MB,Blake CC

    更新日期:1997-10-31 00:00:00

  • Expression and transmission of a rodent retrovirus-like (VL30) gene family.

    abstract::A transcriptionally active sub-set of the dispersed mouse VL30 family of proviral genetic elements was shown to be highly transmissible as a murine leukaemia virus pseudotype. Newly acquired VL30 proviruses (present at 1 to 2 copies per cell) were shown to be transcriptionally active. These data substantiate the hypot...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Carter AT,Norton JD,Gibson Y,Avery RJ

    更新日期:1986-03-05 00:00:00

  • Preliminary X-ray diffraction studies of recombinant 19 kDa human fibroblast collagenase.

    abstract::Crystals of the catalytic domain of human fibroblast collagenase have been grown in the presence and absence of an inhibitor. Crystals of the inhibitor complex grew from 0.2 M ammonium sulfate and 15 to 30% PEG 8000 at 22 degrees C as bipyramids in the space group P6(2) or P6(4). Crystals of the unligated enzyme grew ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Hassell AM,Anderegg RJ,Weigl D,Milburn MV,Burkhart W,Smith GF,Graber P,Wells TN,Luther MA,Jordan SR

    更新日期:1994-03-11 00:00:00

  • Identifying functionally important conformational changes in proteins: activation of the yeast α-factor receptor Ste2p.

    abstract::We have developed a procedure in which disulfide cross-links are used to identify regions of proteins that undergo functionally important intramolecular motion. The approach was applied to the identification of disulfide bonds that stabilize the active state of the yeast α-mating pheromone receptor Ste2p, a member of ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Taslimi A,Mathew E,Celić A,Wessel S,Dumont ME

    更新日期:2012-05-18 00:00:00

  • Burst-phase expansion of native protein prior to global unfolding in SDS.

    abstract::Although numerous studies have been directed at understanding early folding events through the characterization of folding intermediates, there are few reports on the very late folding events, i.e. on the events taking place on the native side of the folding barrier and on alternative conformations of the folded state...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Otzen DE,Oliveberg M

    更新日期:2002-02-01 00:00:00

  • Crystals of threonyl-tRNA synthetase from Thermus thermophilus. Preliminary crystallographic data.

    abstract::Crystals have been obtained of threonyl-tRNA synthetase from the extreme thermophile Thermus thermophilus using sodium formate as a precipitant. The crystals are very stable and diffract to at least 2.4 A. The crystals belong to space group P2(1)2(1)2(1) with cell parameters a = 61.4 A, b = 156.1 A, c = 177.3 A. ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Garber MB,Yaremchuk AD,Tukalo MA,Egorova SP,Fomenkova NP,Nikonov SV

    更新日期:1990-08-20 00:00:00

  • A sparsomycin-resistant mutant of Halobacterium salinarium lacks a modification at nucleotide U2603 in the peptidyl transferase centre of 23 S rRNA.

    abstract::Sparsomycin, a broad-spectrum antibiotic, acts at the peptidyl transferase centre of the ribosome, stabilizing peptidyl-tRNA binding at the P-site and weakening ternary complex binding. A sparsomycin-resistant mutant was isolated for the archaeon Halobacterium salinarium and shown to lack a post-transcriptional modifi...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Lázaro E,Rodriguez-Fonseca C,Porse B,Ureña D,Garrett RA,Ballesta JP

    更新日期:1996-08-16 00:00:00

  • Crystal structure at 1.95 A resolution of the breast tumour-specific antibody SM3 complexed with its peptide epitope reveals novel hypervariable loop recognition.

    abstract::The anti-breast tumour antibody SM3 has a high selectivity in reacting specifically with carcinoma-associated mucin. SM3 recognises the core repeating motif (Pro-Asp-Thr-Arg-Pro) of aberrantly glycosylated epithelial mucin MUC1, and has potential as a therapeutic and diagnostic tool. Here we report the crystal structu...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Dokurno P,Bates PA,Band HA,Stewart LM,Lally JM,Burchell JM,Taylor-Papadimitriou J,Snary D,Sternberg MJ,Freemont PS

    更新日期:1998-12-04 00:00:00

  • Formation of the gap junction intercellular channel requires a 30 degree rotation for interdigitating two apposing connexons.

    abstract::Intercellular communication via gap junction membrane channels cannot occur until two apposing hemichannels (connexons) meet and dock to form a sealed cell-cell conduit. In particular, an important question is how does the structure at the extracellular surface influence the molecular recognition of the two connexons....

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Perkins GA,Goodenough DA,Sosinsky GE

    更新日期:1998-03-27 00:00:00