Abstract：
: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.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Pfuhl M,Winder SJ,Castiglione Morelli MA,Labeit S,Pastore Adoi
10.1006/jmbi.1996.0169subject
Has Abstractpub_date
1996-03-29 00:00:00pages
367-84issue
2eissn
0022-2836issn
1089-8638pii
S0022-2836(96)90169-2journal_volume
257pub_type
杂志文章abstract：:Induction of gene expression has great potential in the treatment of many human diseases. Peptide nucleic acid (PNA) as a novel DNA-binding reagent provides an ideal system to induce gene-specific expression. In our recent studies, we have demonstrated that PNA bound to double-stranded DNA targets and, therefore, gene...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2001.5109
更新日期：2001-11-09 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2004.10.046
更新日期：2005-01-14 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2001.5260
更新日期：2002-01-25 00:00:00
abstract：:Residues specifying aminoacylation by yeast tyrosyl-tRNA synthetase (TyrRS) of the tRNA-like structure present at the 3'-end of brome mosaic virus (BMV) RNA were determined by the in vitro approach using phage T7 transcripts. They correspond to nucleotides equivalent to base-pair C1-G72 and discriminator base A73 in t...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2001.4654
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1999.2569
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(88)90438-x
更新日期：1988-05-05 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.2429
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1997.1545
更新日期：1998-02-20 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2000.3619
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2011.08.048
更新日期：2011-10-28 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(85)90209-8
更新日期：1985-05-25 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2011.06.035
更新日期：2011-09-02 00:00:00
abstract：:Cyclin K and the closely related cyclins T1, T2a, and T2b interact with cyclin-dependent kinase 9 (CDK9) forming multiple nuclear complexes, referred to collectively as positive transcription elongation factor b (P-TEFb). Through phosphorylation of the C-terminal domain of the RNA polymerase II largest subunit, distin...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2006.11.057
更新日期：2007-02-16 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2003.11.038
更新日期：2004-01-30 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2012.08.014
更新日期：2012-11-02 00:00:00
abstract：:The trigger factor is associated with bacterial ribosomes and catalyzes proline-limited protein folding reactions. Its folding activity is very high and conserved in evolution, as shown for the homologous enzymes from Escherichia coli and Mycoplasma genitalium. The folding protein substrate (a variant of ribonuclease ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1997.1604
更新日期：1998-04-03 00:00:00
abstract：:A database of X-ray crystal structures of double helical DNA oligomers has been used to analyse the role of the sugar-phosphate backbone in coupling the conformational properties of neighbouring dinucleotide steps. The base step parameters which are most strongly coupled to the backbone degrees of freedom are slide an...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1999.3237
更新日期：2000-01-07 00:00:00
abstract：:The attempt is made to find new correlations between local structural characteristics of proteins and the hydrogen exchange rates of their individual main-chain amides, and to relate such correlations to possible mechanisms of hydrogen exchange. It is found that in bovine pancreatic trypsin inhibitor (BPTI) the surfac...
journal_title：Journal of molecular biology
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更新日期：1987-11-20 00:00:00
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journal_title：Journal of molecular biology
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1996.0844
更新日期：1997-03-14 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1994.1152
更新日期：1994-02-18 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
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更新日期：2005-02-18 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2005.01.066
更新日期：2005-04-22 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(90)90148-F
更新日期：1990-07-05 00:00:00
abstract：:The segment of the vaccinia DNA topoisomerase from residues 143 to 167 (VGLLTLKNKHIEISPDEIVIKFVGK) is conserved in other members of the eukaryotic type I topoisomerase family. In order to gauge the function of this region, we performed a mutational analysis in which 23 of 25 positions were substituted by alanine. Seve...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1996.0568
更新日期：1996-10-25 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2000.4048
更新日期：2000-09-08 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2018.08.023
更新日期：2018-10-19 00:00:00
abstract：:The oxyR-encoded regulatory protein, OxyR, acts to induce the synthesis of a family of hydrogen peroxide-inducible proteins in Salmonella typhimurium and Escherichia coli. To further define the mechanism by which oxyR regulates the production of these proteins, we identified, mapped, and characterized oxyR-regulated p...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(89)90104-6
更新日期：1989-12-20 00:00:00
