Moderated Poster Session - Heart245The involvement of TWEAK and FN14 in murine autoimmune myocarditis246Sympathetic neurons that innervate the heart locally modulate cardiomyocyte trophic and electrophysiological properties247W4R variant of CSRP3 leads to the expression of a novel alternate reading frame protein due to alternative splicing248Glucocorticoid intervention prenatally: effects on fetal heart maturation249Uncoupling of myofilament Ca2+-sensitivity from troponin I phosphorylation by hypertrophic

Fischer, Andreas; Pianca, Nicola; Azzimato, Valerio; Batchen, Emma; Messer, Andrew E.; Jehuda, Ronen Ben; Mueller, AM; Bangert, Anna; Bockstahler, Mariella; Oettl, R; Katus, HA; Kaya, Ziya; Prando, Valentina; Franzoso, Mauro; Bona, Anna Di; Campione, Marina; Sandri, Monica; Zaglia, Tania; Mongillo, Marco; Tabish, AM; Buyandelger, Byambajav; Enesa, KN; Hunt, Judson; Milner, Rowan J.; Wiseman, John; Wahlgren, J; Bohlooly, Mohammad; Knoell, Ralph; Richardson, Rachel; Thomson, Adrian; Moran, Carlos M.; Gray, Gillian A.; Chapman, Karen; Papadaki, Maria; Vikhorev, PG; Sheehan, Alice; Marston, S; Hallas, Tova; Haykain, T; Eisen, Binyamin; Schick, Revital; Gherghiceanu, Mihaela; Mandel, Hanna; Arad, Michael; Binah, O.

doi:10.1093/cvr/cvw132

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…R145G increased the interaction between Ca 2+ and Ser69 GO explaining the increased Ca 2+ binding. On the other hand, these interactions were not observed in Zamora's analysis and the most evident effect of the mutations TnI R145G (HCM), TnI K36Q, and TnC G159D (both DCM) is that they trap Ser69 GO in the short distance configuration (Sheehan et al, 2016; Zamora et al, 2016b). …”

Section: Insights For Troponin Regulatory Mechanismmentioning

confidence: 98%

The Importance of Intrinsically Disordered Segments of Cardiac Troponin in Modulating Function by Phosphorylation and Disease-Causing Mutations

Papadaki

Marston

2016

Front. Physiol.

View full text Add to dashboard Cite

Troponin plays a central role in regulation of muscle contraction. It is the Ca2+ switch of striated muscles including the heart and in the cardiac muscle it is physiologically modulated by PKA-dependent phosphorylation at Ser22 and 23. Many cardiomyopathy-related mutations affect Ca2+ regulation and/or disrupt the relationship between Ca2+ binding and phosphorylation. Unlike the mechanism of heart activation, the modulation of Ca2+-sensitivity by phosphorylation of the cardiac specific N-terminal segment of TnI (1–30) is structurally subtle and has proven hard to investigate. The crystal structure of cardiac troponin describes only the relatively stable core of the molecule and the crucial mobile parts of the molecule are missing including TnI C-terminal region, TnI (1–30), TnI (134–149) (“inhibitory” peptide) and the C-terminal 28 amino acids of TnT that are intrinsically disordered. Recent studies have been performed to answer this matter by building structural models of cardiac troponin in phosphorylated and dephosphorylated states based on peptide NMR studies. Now these have been updated by more recent concepts derived from molecular dynamic simulations treating troponin as a dynamic structure. The emerging model confirms the stable core structure of troponin and the mobile structure of the intrinsically disordered segments. We will discuss how we can describe these segments in terms of dynamic transitions between a small number of states, with the probability distributions being altered by phosphorylation and by HCM or DCM-related mutations that can explain how Ca2+-sensitivity is modulated by phosphorylation and the effects of mutations.

show abstract

Section: Insights For Troponin Regulatory Mechanismmentioning

confidence: 98%

The Importance of Intrinsically Disordered Segments of Cardiac Troponin in Modulating Function by Phosphorylation and Disease-Causing Mutations

Papadaki

Marston

2016

Front. Physiol.

View full text Add to dashboard Cite

show abstract

Cited by 1 publication

References 0 publications

The Importance of Intrinsically Disordered Segments of Cardiac Troponin in Modulating Function by Phosphorylation and Disease-Causing Mutations

The Importance of Intrinsically Disordered Segments of Cardiac Troponin in Modulating Function by Phosphorylation and Disease-Causing Mutations

Contact Info

Product

Resources

About