دورية أكاديمية
Enhanced troponin I binding explains the functional changes produced by the hypertrophic cardiomyopathy mutation A8V of cardiac troponin C.
| العنوان: | Enhanced troponin I binding explains the functional changes produced by the hypertrophic cardiomyopathy mutation A8V of cardiac troponin C. |
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| المساهمون: | Zot, Henry G (authoraut), Hasbun, Javier E (authoraut), Michell, Clara A (authoraut), Landim-Vieira, Maicon (authoraut), Pinto, Jose R (authoraut) |
| المجموعة: | Florida State University Digital Library (FSUDL) |
| مصطلحات موضوعية: | Adenosine Triphosphatases/chemistry, Calcium/chemistry, Cardiomyopathy, Hypertrophic/genetics, Hypertrophic/metabolism, Humans, Imaging, Three-Dimensional, Microscopy, Fluorescence, Mutation, Myocardial Contraction, Myocardium/metabolism, Myofibrils/chemistry, Protein Binding, Protein Domains, Recombinant Proteins/chemistry, Troponin C/chemistry, Troponin C/genetics, Troponin I/chemistry, Troponin I/genetics |
| الوصف: | Higher affinity for TnI explains how troponin C (TnC) carrying a causative hypertrophic cardiomyopathy mutation, TnC(A8V), sensitizes muscle cells to Ca(2+). Muscle fibers reconstituted with TnC(A8V) require ∼2.3-fold less [Ca(2+)] to achieve 50% maximum-tension compared to fibers reconstituted with wild-type TnC (TnC(WT)). Binding measurements rule out a significant change in N-terminus Ca(2+)-affinity of isolated TnC(A8V), and TnC(A8V) binds the switch-peptide of troponin-I (TnI(sp)) ∼1.6-fold more strongly than TnC(WT); thus we model the TnC-TnI(sp) interaction as competing with the TnI-actin interaction. Tension data are well-fit by a model constrained to conditions in which the affinity of TnC(A8V) for TnI(sp) is 1.5-1.7-fold higher than that of TnC(WT) at all [Ca(2+)]. Mean ATPase rates of reconstituted cardiac myofibrils is greater for TnC(A8V) than TnC(WT) at all [Ca(2+)], with statistically significant differences in the means at higher [Ca(2+)]. To probe TnC-TnI interaction in low Ca(2+), displacement of bis-ANS from TnI was monitored as a function of TnC. Whereas Ca(2+)-TnC(WT) displaces significantly more bis-ANS than Mg(2+)-TnC(WT), Ca(2+)-TnC(A8V) displaces probe equivalently to Mg(2+)-TnC(A8V) and Ca(2+)-TnC(WT), consistent with stronger Ca(2+)-independent TnC(A8V)-TnI(sp). A Matlab program for computing theoretical activation is reported. Our work suggests that contractility is constantly above normal in hearts made hypertrophic by TnC(A8V). ; Cardiac troponin C, Fluorescence, Hypertrophic cardiomyopathy, Modeling, Myofibrillar ATPase, Troponin I binding ; K99 HL103840, R00 HL103840 ; This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899184Test. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 1 online resource; computer; application/pdf |
| اللغة: | English |
| العلاقة: | Archives of biochemistry and biophysics--1096-0384--1096-0384 |
| DOI: | 10.1016/j.abb.2016.03.011 |
| الإتاحة: | https://doi.org/10.1016/j.abb.2016.03.011Test http://purl.flvc.org/fsu/fd/FSU_pmch_26976709Test http://fsu.digital.flvc.org/islandora/object/fsu%3A523967/datastream/TN/view/Enhanced%20troponin%20I%20binding%20explains%20the%20functional%20changes%20produced%20by%20the%20hypertrophic%20cardiomyopathy%20mutation%20A8V%20of%20cardiac%20troponin%20C.jpgTest |
| رقم الانضمام: | edsbas.1439E6F6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.abb.2016.03.011 |
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