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














  • X-ray diffraction and electron microscopy from Lethocerus flight muscle partially relaxed by adenylylimidodiphosphate and ethylene glycol.

    abstract::The low-angle X-ray diffraction pattern from Lethocerus flight muscle fibres was recorded in rigor or under two conditions that modify crossbridge structure and behaviour, aqueous adenylylimidodiphosphate (AMPPNP) and AMPPNP + calcium in an ethylene glycol-water mixture. The effects on the 38.7 nm layer-line peaks (hk...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Tregear RT,Wakabayashi K,Tanaka H,Iwamoto H,Reedy MC,Reedy MK,Sugi H,Amemiya Y

    更新日期:1990-07-05 00:00:00

  • X-ray crystal structure of a non-crystalline cellulose-specific carbohydrate-binding module: CBM28.

    abstract::Natural cellulose exists as a composite of different forms, which have historically been broadly characterized as "crystalline" or "amorphous". The recognition of both of these forms of cellulose by the carbohydrate-binding modules (CBM) of microbial glycoside hydrolases is central to natural and efficient biotechnolo...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Jamal S,Nurizzo D,Boraston AB,Davies GJ

    更新日期:2004-05-28 00:00:00

  • Engineering GST M2-2 for high activity with indene 1,2-oxide and indication of an H-site residue sustaining catalytic promiscuity.

    abstract::The substrate-binding H-site of human glutathione transferase (GST) M2-2 was subjected to iterative saturation mutagenesis in order to obtain an efficient enzyme with the novel epoxide substrate indene 1,2-oxide. Residues 10, 116, and 210 were targeted, and the activities with the alternative substrates, benzyl isothi...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Norrgård MA,Mannervik B

    更新日期:2011-09-09 00:00:00

  • Multi-timescale dynamics study of FKBP12 along the rapamycin-mTOR binding coordinate.

    abstract::Drugs can affect function in proteins by modulating their flexibility. Despite this possibility, there are very few studies on how drug binding affects the dynamics of target macromolecules. FKBP12 (FK506 binding protein 12) is a prolyl cis-trans isomerase and a drug target. The immunosuppressant drug rapamycin exerts...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Sapienza PJ,Mauldin RV,Lee AL

    更新日期:2011-01-14 00:00:00

  • Integrated Use of Biochemical, Native Mass Spectrometry, Computational, and Genome-Editing Methods to Elucidate the Mechanism of a Salmonella deglycase.

    abstract::Salmonellais a foodborne pathogen that causes annually millions of cases of salmonellosis globally, yet Salmonella-specific antibacterials are not available. During inflammation, Salmonella utilizes the Amadori compound fructose-asparagine (F-Asn) as a nutrient through the successive action of three enzymes, including...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Sengupta A,Wu J,Seffernick JT,Sabag-Daigle A,Thomsen N,Chen TH,Capua AD,Bell CE,Ahmer BMM,Lindert S,Wysocki VH,Gopalan V

    更新日期:2019-11-08 00:00:00

  • FlgB, FlgC, FlgF and FlgG. A family of structurally related proteins in the flagellar basal body of Salmonella typhimurium.

    abstract::The flagellar basal body of Salmonella typhimurium consists of four rings surrounding a rod. The rod, which is believed to transmit motor rotation to the filament, is not well characterized in terms of its structure and composition. FlgG is known to lie within the distal portion of the rod, in the region where it is s...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Homma M,Kutsukake K,Hasebe M,Iino T,Macnab RM

    更新日期:1990-01-20 00:00:00

  • Primary organization of nucleosomes. Interaction of non-histone high mobility group proteins 14 and 17 with nucleosomes, as revealed by DNA-protein crosslinking and immunoaffinity isolation.

    abstract::The binding sites for histones and high mobility group proteins (HMG) 14 and 17 have been located on DNA in the nucleosomal cores and H1/H5-containing nucleosomes. The nucleosomes were specifically associated with two molecules of the non-histone proteins HMG 14 and/or HMG 17 when followed by DNA-protein crosslinking ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Shick VV,Belyavsky AV,Mirzabekov AD

    更新日期:1985-09-20 00:00:00

  • The structure of deoxy- and oxy-leghaemoglobin from lupin.

    abstract::The leghaemoglobins have oxygen affinities 11 to 24 times higher than that of sperm whale myoglobin, due mainly to higher rates of association. To find out why, we have determined the structures of deoxy- and oxy-leghaemoglobin II of the lupin at 1.7 A resolution. Results confirm the general features found in previous...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Harutyunyan EH,Safonova TN,Kuranova IP,Popov AN,Teplyakov AV,Obmolova GV,Rusakov AA,Vainshtein BK,Dodson GG,Wilson JC

    更新日期:1995-08-04 00:00:00

  • Isolation and nucleotide sequence analysis of the beta-type globin pseudogene from human, gorilla and chimpanzee.

    abstract::The beta-globin gene cluster of human, gorilla and chimpanzee contain the same number and organization of beta-type globin genes: 5'-epsilon (embryonic)-G gamma and A gamma (fetal)-psi beta (inactive)-delta and beta (adult)-3'. We have isolated the psi beta-globin gene regions from the three species and determined the...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Chang LY,Slightom JL

    更新日期:1984-12-25 00:00:00

  • Morphology of sheet-like assemblies of pN-collagen, pC-collagen and procollagen studied by scanning transmission electron microscopy mass measurements.

    abstract::At high concentrations, type I pN-collagen, pC-collagen and procollagen (the first 2 generated from procollagen by enzymic cleavage of C-propeptides and N-propeptides, respectively) can all be made to assemble in vitro into thin D-periodic sheets or tapes. Scanning transmission electron microscopy mass measurements sh...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Holmes DF,Mould AP,Chapman JA

    更新日期:1991-07-05 00:00:00

  • Protein-DNA interactions: amino acid conservation and the effects of mutations on binding specificity.

    abstract::We investigate the conservation of amino acid residue sequences in 21 DNA-binding protein families and study the effects that mutations have on DNA-sequence recognition. The observations are best understood by assigning each protein family to one of three classes: (i) non-specific, where binding is independent of DNA ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Luscombe NM,Thornton JM

    更新日期:2002-07-26 00:00:00

  • Site-directed mutagenesis on human cystathionine-gamma-lyase reveals insights into the modulation of H2S production.

    abstract::In recent years, increased interest has been directed towards hydrogen sulfide (H2S) as the third gasotransmitter and its role in various diseases. Cystathionine-gamma-lyase (CSE) is one of the enzymes responsible for the endogenous production of H2S in mammals. With the aid of the crystal structures of human CSE and ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Huang S,Chua JH,Yew WS,Sivaraman J,Moore PK,Tan CH,Deng LW

    更新日期:2010-02-26 00:00:00

  • Local folding coupled to RNA binding in the yeast ribosomal protein L30.

    abstract::The ribosomal protein L30 from yeast Saccharomyces cerevisiae auto-regulates its own synthesis by binding to a structural element in both its pre-mRNA and its mRNA. The three-dimensional structures of L30 in the free (f L30) and the pre-mRNA bound (b L30) forms have been solved by nuclear magnetic resonance spectrosco...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Mao H,Williamson JR

    更新日期:1999-09-17 00:00:00

  • Titin organisation and the 3D architecture of the vertebrate-striated muscle I-band.

    abstract::The giant muscle protein titin (connectin) is known to serve as a cytoskeletal element in muscle sarcomeres. It elastically restrains lengthening sarcomeres, it aids the integrity and central positioning of the A-band in the sarcomere and it may act as a template upon which some sarcomeric components are laid down dur...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Knupp C,Luther PK,Squire JM

    更新日期:2002-09-27 00:00:00

  • Alkaline Bohr effect of human hemoglobin Ao.

    abstract::Differential oxygen binding measurements obtained over the pH range 6.95 to 9.10 at 25 degrees C have allowed a detailed description of the alkaline Bohr effect of human hemoglobin Ao. Phenomenological analysis of the data in terms of the Adair equation shows that: (1) the oxygen binding curves are asymmetrical with t...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Di Cera E,Doyle ML,Gill SJ

    更新日期:1988-04-05 00:00:00

  • Context-dependent remodeling of structure in two large protein fragments.

    abstract::Protein folding involves the formation of secondary structural elements from the primary sequence and their association with tertiary assemblies. The relation of this primary sequence to a specific folded protein structure remains a central question in structural biology. An increasing body of evidence suggests that v...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Schellenberg MJ,Ritchie DB,Wu T,Markin CJ,Spyracopoulos L,MacMillan AM

    更新日期:2010-10-01 00:00:00

  • Three-dimensional solid-state NMR study of a seven-helical integral membrane proton pump--structural insights.

    abstract::Proteorhodopsin (PR) is a recently discovered ubiquitous eubacterial retinal-binding light-driven proton pump. Almost 1000 PR variants are widely distributed in species of marine and freshwater bacteria, suggesting PR's important photobiological role. PR is a typical seven-transmembrane alpha-helical membrane protein ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Shi L,Ahmed MA,Zhang W,Whited G,Brown LS,Ladizhansky V

    更新日期:2009-03-06 00:00:00

  • Mapping transition states of protein unfolding by protein engineering of ligand-binding sites.

    abstract::We describe a method for probing the integrity and relative orientation of structural elements that are indirectly linked by ligands in protein complexes during protein folding. The effect of 3'-GMP on the rate constants of unfolding of wild-type barnase and several mutants has been studied. By comparing the rates of ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Sancho J,Meiering EM,Fersht AR

    更新日期:1991-10-05 00:00:00

  • Detecting patterns in protein sequences.

    abstract::The detection of conserved sequence patterns (motifs) in related proteins often yields valuable structural and functional insights. We describe a method that utilizes rigorous statistics and a depth-first search procedure to efficiently and exhaustively search a set of proteins for significant patterns up to a specifi...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Neuwald AF,Green P

    更新日期:1994-06-24 00:00:00

  • Location of high and low affinity fatty acid binding sites on human serum albumin revealed by NMR drug-competition analysis.

    abstract::Human serum albumin (HSA) is an abundant plasma protein that transports a wide variety of drugs and endogenous compounds. The complex binding capacity of HSA has made it a challenging system to study in detail but in order to develop our understanding of the interactions between ligands for HSA, the locations and rela...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Simard JR,Zunszain PA,Hamilton JA,Curry S

    更新日期:2006-08-11 00:00:00

  • The central PPT of the yeast retrotransposon Ty1 is not essential for transposition.

    abstract::The yeast retrotransposon Ty1 has structural and functional similarities to retroviruses. We report here that, as in retroviruses, the plus-strand DNA of Ty1 is synthesized as two segments. A central DNA flap is formed during reverse transcription consecutive to elongation (with strand displacement) of the upstream se...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Heyman T,Wilhelm M,Wilhelm FX

    更新日期:2003-08-08 00:00:00

  • Fragment ranking in modelling of protein structure. Conformationally constrained environmental amino acid substitution tables.

    abstract::Conformationally constrained environment-dependent amino acid residue substitution tables have been constructed from a database comprising 33 homologous families of protein sequences aligned on the basis of their three-dimensional structures. Residues are allotted to one of 216 (or 54) classes of combinations of struc...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Topham CM,McLeod A,Eisenmenger F,Overington JP,Johnson MS,Blundell TL

    更新日期:1993-01-05 00:00:00

  • DJ-1 protects dopaminergic neurons against rotenone-induced apoptosis by enhancing ERK-dependent mitophagy.

    abstract::Loss-of-function mutations in the gene encoding the multifunctional protein, DJ-1, have been implicated in the pathogenesis of early-onset familial Parkinson's disease (PD), suggesting that DJ-1 may act as a neuroprotectant for dopaminergic (DA) neurons. Enhanced autophagy may benefit PD by clearing damaged organelles...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Gao H,Yang W,Qi Z,Lu L,Duan C,Zhao C,Yang H

    更新日期:2012-10-19 00:00:00

  • Replication of mini RK2 plasmid in extracts of Escherichia coli requires plasmid-encoded protein TrfA and host-encoded proteins DnaA, B, G DNA gyrase and DNA polymerase III.

    abstract::Soluble extracts of Escherichia coli capable of carrying out replication of the mini-RK2 derivative pCT461 have been prepared from cells carrying this plasmid or from plasmid-free bacteria. The latter are dependent upon exogenously added plasmid-encoded replication protein (TrfA) and require additional DnaA protein fo...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Pinkney M,Diaz R,Lanka E,Thomas CM

    更新日期:1988-10-20 00:00:00

  • Erythromycin-induced stabilization of ermA messenger RNA in Staphylococcus aureus and Bacillus subtilis.

    abstract::Erythromycin-induced stabilization of ermA mRNA was studied in Staphylococcus aureus, its original host background, and in Bacillus subtilis, subcloned on plasmid vectors. By RNA blot analysis it was shown that 40 nM-erythromycin specifically increased the chemical half-life of ermA mRNA from 2.5 to 17.5 minutes where...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Sandler P,Weisblum B

    更新日期:1988-10-20 00:00:00

  • TissueCoCoPUTs: Novel Human Tissue-Specific Codon and Codon-Pair Usage Tables Based on Differential Tissue Gene Expression.

    abstract::Protein expression in multicellular organisms varies widely across tissues. Codon usage in the transcriptome of each tissue is derived from genomic codon usage and the relative expression level of each gene. We created a comprehensive computational resource that houses tissue-specific codon, codon-pair, and dinucleoti...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Kames J,Alexaki A,Holcomb DD,Santana-Quintero LV,Athey JC,Hamasaki-Katagiri N,Katneni U,Golikov A,Ibla JC,Bar H,Kimchi-Sarfaty C

    更新日期:2020-05-15 00:00:00

  • Coordinated transcriptional regulation of Hspa1a gene by multiple transcription factors: crucial roles for HSF-1, NF-Y, NF-κB, and CREB.

    abstract::Although the transcript level of inducible heat shock protein 70.3 (Hsp70.3, also known as Hspa1a) is altered in various disease states, its transcriptional regulation remains incompletely understood. Here, we systematically analyzed the Hspa1a promoter to identify major cis elements and transcription factors that may...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Sasi BK,Sonawane PJ,Gupta V,Sahu BS,Mahapatra NR

    更新日期:2014-01-09 00:00:00

  • Functional analysis of the glucocorticoid regulatory elements present in the mouse mammary tumor virus long terminal repeat. A synthetic distal binding site can replace the proximal binding domain.

    abstract::Transcription of mouse mammary tumor virus DNA is stimulated by steroid hormones. The DNA sequences involved in this regulation are located in the viral long terminal repeat between positions -200 and -50 with respect to the transcription initiation site. In this region four, one distal and three proximal, in vitro bi...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Kühnel B,Buetti E,Diggelmann H

    更新日期:1986-08-05 00:00:00

  • The positive transcription elongation factor b is an essential cofactor for the activation of transcription by myocyte enhancer factor 2.

    abstract::The positive transcription elongation factor b (P-TEFb), composed of cyclin-dependent kinase 9 and cyclin T1, stimulates the elongation of transcription by hyperphosphorylating the C-terminal region of RNA polymerase II. Aberrant activation of P-TEFb results in manifestations of cardiac hypertrophy in mice, suggesting...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Nojima M,Huang Y,Tyagi M,Kao HY,Fujinaga K

    更新日期:2008-10-03 00:00:00

  • Structure of Mutant Hepatitis B Core Protein Capsids with Premature Secretion Phenotype.

    abstract::Hepatitis B virus is a major human pathogen that consists of a viral genome surrounded by an icosahedrally ordered core protein and a polymorphic, lipidic envelope that is densely packed with surface proteins. A point mutation in the core protein in which a phenylalanine at position 97 is exchanged for a smaller leuci...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Böttcher B,Nassal M

    更新日期:2018-12-07 00:00:00