You are here

Role of cardiac troponin I carboxy terminal mobile domain and linker sequence in regulating cardiac contraction.

Title: Role of cardiac troponin I carboxy terminal mobile domain and linker sequence in regulating cardiac contraction.
6 views
0 downloads
Name(s): Meyer, Nancy L, author
Chase, P Bryant, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2016-07-01
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Inhibition of striated muscle contraction at resting Ca(2+) depends on the C-terminal half of troponin I (TnI) in thin filaments. Much focus has been on a short inhibitory peptide (Ip) sequence within TnI, but structural studies and identification of disease-associated mutations broadened emphasis to include a larger mobile domain (Md) sequence at the C-terminus of TnI. For Md to function effectively in muscle relaxation, tight mechanical coupling to troponin's core-and thus tropomyosin-is presumably needed. We generated recombinant, human cardiac troponins containing one of two TnI constructs: either an 8-amino acid linker between Md and the rest of troponin (cTnILink8), or an Md deletion (cTnI1-163). Motility assays revealed that Ca(2+)-sensitivity of reconstituted thin filament sliding was markedly increased with cTnILink8 (∼0.9 pCa unit leftward shift of speed-pCa relation compared to WT), and increased further when Md was missing entirely (∼1.4 pCa unit shift). Cardiac Tn's ability to turn off filament sliding at diastolic Ca(2+) was mostly (61%), but not completely eliminated with cTnI1-163. TnI's Md is required for full inhibition of unloaded filament sliding, although other portions of troponin-presumably including Ip-are also necessary. We also confirm that TnI's Md is not responsible for superactivation of actomyosin cycling by troponin.
Identifier: FSU_pmch_26971468 (IID), 10.1016/j.abb.2016.03.010 (DOI), PMC4899117 (PMCID), 26971468 (RID), 26971468 (EID), S0003-9861(16)30062-5 (PII)
Keywords: Calcium, Excitation-contraction coupling, Heart, In vitro motility assay, Thin filament, Unloaded filament sliding
Grant Number: R01 HL063974
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899117.
Subject(s): Actin Cytoskeleton/metabolism
Actins/metabolism
Actomyosin/chemistry
Animals
Calcium/chemistry
Humans
Muscle Relaxation/drug effects
Muscle, Skeletal/metabolism
Mutation
Myocardial Contraction
Myocardium/metabolism
Protein Domains
Rabbits
Recombinant Proteins/chemistry
Stress, Mechanical
Tropomyosin/chemistry
Troponin I/chemistry
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_26971468
Owner Institution: FSU
Is Part Of: Archives of biochemistry and biophysics.
1096-0384
Issue: vol. 601

Choose the citation style.
Meyer, N. L., & Chase, P. B. (2016). Role of cardiac troponin I carboxy terminal mobile domain and linker sequence in regulating cardiac contraction. Archives Of Biochemistry And Biophysics. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_26971468