scholarly journals Genomic Organization, Expression, and Analysis of the Troponin C Gene pat-10 of Caenorhabditis elegans

1999 ◽  
Vol 146 (1) ◽  
pp. 193-202 ◽  
Author(s):  
Hiromi Terami ◽  
Benjamin D. Williams ◽  
Shin-ichi Kitamura ◽  
Yasuji Sakube ◽  
Shinji Matsumoto ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Calcium Binding ◽  
Troponin I ◽  
Amino Acid Level ◽  
Troponin C ◽  
In Vivo Studies ◽  
Calcium Binding Site ◽  
Expression Studies ◽  
Missense Alteration

We have cloned and characterized the troponin C gene, pat-10 of the nematode Caenorhabditis elegans. At the amino acid level nematode troponin C is most similar to troponin C of Drosophila (45% identity) and cardiac troponin C of vertebrates. Expression studies demonstrate that this troponin is expressed in body wall muscle throughout the life of the animal. Later, vulval muscles and anal muscles also express this troponin C isoform. The structural gene for this troponin is pat-10 and mutations in this gene lead to animals that arrest as twofold paralyzed embryos late in development. We have sequenced two of the mutations in pat-10 and both had identical two mutations in the gene; one changes D64 to N and the other changes W153 to a termination site. The missense alteration affects a calcium-binding site and eliminates calcium binding, whereas the second mutation eliminates binding to troponin I. These combined biochemical and in vivo studies of mutant animals demonstrate that this troponin is essential for proper muscle function during development.

scholarly journals Atomic resolution probe for allostery in the regulatory thin filament

2016 ◽  
Vol 113 (12) ◽  
pp. 3257-3262 ◽  
Author(s):  
Michael R. Williams ◽  
Sarah J. Lehman ◽  
Jil C. Tardiff ◽  
Steven D. Schwartz
Keyword(s):  
Binding Site ◽  
Human Disease ◽  
Calcium Binding ◽  
Cardiac Troponin ◽  
Thin Filament ◽  
Troponin I ◽  
Troponin T ◽  
Calcium Binding Site

Calcium binding and dissociation within the cardiac thin filament (CTF) is a fundamental regulator of normal contraction and relaxation. Although the disruption of this complex, allosterically mediated process has long been implicated in human disease, the precise atomic-level mechanisms remain opaque, greatly hampering the development of novel targeted therapies. To address this question, we used a fully atomistic CTF model to test both Ca2+ binding strength and the energy required to remove Ca2+ from the N-lobe binding site in WT and mutant troponin complexes that have been linked to genetic cardiomyopathies. This computational approach is combined with measurements of in vitro Ca2+ dissociation rates in fully reconstituted WT and cardiac troponin T R92L and R92W thin filaments. These human disease mutations represent known substitutions at the same residue, reside at a significant distance from the calcium binding site in cardiac troponin C, and do not affect either the binding pocket affinity or EF-hand structure of the binding domain. Both have been shown to have significantly different effects on cardiac function in vivo. We now show that these mutations independently alter the interaction between the Ca2+ ion and cardiac troponin I subunit. This interaction is a previously unidentified mechanism, in which mutations in one protein of a complex indirectly affect a third via structural and dynamic changes in a second to yield a pathogenic change in thin filament function that results in mutation-specific disease states. We can now provide atom-level insight that is potentially highly actionable in drug design.

scholarly journals Crystallization of a synthetic analog of calcium-binding site III of rabbit skeletal troponin C

1989 ◽  
Vol 264 (17) ◽  
pp. 10261-10263
Author(s):  
L T J Delbaere ◽  
M Vandonselaar ◽  
R E Reid
Keyword(s):  
Binding Site ◽  
Calcium Binding ◽  
Troponin C ◽  
Synthetic Analog ◽  
Calcium Binding Site

ChemInform Abstract: Benzofuran-Chalcone Hybrids as Potential Multifunctional Agents Against Alzheimer′s Disease: Synthesis and in vivo Studies with Transgenic Caenorhabditis elegans.

ChemInform ◽  
2015 ◽  
Vol 46 (18) ◽  
pp. no-no
Author(s):  
Koneni V. Sashidhara ◽  
Ram K. Modukuri ◽  
Pooja Jadiya ◽  
Ranga Prasad Dodda ◽  
Manoj Kumar ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
In Vivo Studies ◽  
Multifunctional Agents

scholarly journals Interaction between Troponin C and Troponin I of body wall in Caenorhabditis elegans

2003 ◽  
Vol 43 (supplement) ◽  
pp. S122
Author(s):  
M. Soda ◽  
T. Takaya ◽  
H. Kagawa ◽  
T. Iio
Keyword(s):  
Caenorhabditis Elegans ◽  
Body Wall ◽  
Troponin I ◽  
Troponin C

scholarly journals 2P169 Molecular interaction between two troponin C and four troponin I of Caenorhabditis elegans

2005 ◽  
Vol 45 (supplement) ◽  
pp. S162
Author(s):  
Ziaul Amin ◽  
Razia Ruksana ◽  
T. Takaya ◽  
H. Kagawa
Keyword(s):  
Caenorhabditis Elegans ◽  
Molecular Interaction ◽  
Troponin I ◽  
Troponin C

scholarly journals Importance of Calcium-Binding Site 2 in Simian Virus 40 Infection

2007 ◽  
Vol 81 (11) ◽  
pp. 6099-6105 ◽  
Author(s):  
Peggy P. Li ◽  
Albert P. Nguyen ◽  
Qiumin Qu ◽  
Qumber H. Jafri ◽  
Saharat Aungsumart ◽  
...  
Keyword(s):  
Binding Site ◽  
Calcium Binding ◽  
Simian Virus 40 ◽  
Antigen Expression ◽  
Simian Virus ◽  
T Antigen ◽  
Calcium Binding Site ◽  
Viral Dna ◽  
Particle Assembly

ABSTRACT The exposure of molecular signals for simian virus 40 (SV40) cell entry and nuclear entry has been postulated to involve calcium coordination at two sites on the capsid made of Vp1. The role of calcium-binding site 2 in SV40 infection was examined by analyzing four single mutants of site 2, the Glu160Lys, Glu160Arg, Glu157Lys (E157K), and Glu157Arg mutants, and an E157K-E330K combination mutant. The last three mutants were nonviable. All mutants replicated viral DNA normally, and all except the last two produced particles containing all three capsid proteins and viral DNA. The defect of the site 1-site 2 E157K-E330K double mutant implies that at least one of the sites is required for particle assembly in vivo. The nonviable E157K particles, about 10% larger in diameter than the wild type, were able to enter cells but did not lead to T-antigen expression. Cell-internalized E157K DNA effectively coimmunoprecipitated with anti-Vp1 antibody, but little of the DNA did so with anti-Vp3 antibody, and none was detected in anti-importin immunoprecipitate. Yet, a substantial amount of Vp3 was present in anti-Vp1 immune complexes, suggesting that internalized E157K particles are ineffective at exposing Vp3. Our data show that E157K mutant infection is blocked at a stage prior to the interaction of the Vp3 nuclear localization signal with importins, consistent with a role for calcium-binding site 2 in postentry steps leading to the nuclear import of the infecting SV40.

scholarly journals 1E1330 Calcium-binding of pharyngeal muscle troponin C of Caenorhabditis elegans

2002 ◽  
Vol 42 (supplement2) ◽  
pp. S31
Author(s):  
M. Soda ◽  
H. Terami ◽  
H. Kagawa ◽  
T. Iio
Keyword(s):  
Caenorhabditis Elegans ◽  
Calcium Binding ◽  
Troponin C ◽  
Pharyngeal Muscle
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