We investigated structural and functional aspects of the first mutation in 
TNNC1, coding for the calcium-binding subunit (cTnC) of cardiac troponin, which 
was detected in a patient with hypertrophic cardiomyopathy [ Hoffmann B, 
Schmidt-Traub H, Perrot A, Osterziel KJ & Gessner R (2001) Hum Mut17, 524]. This 
mutation leads to a leucine-glutamine exchange at position 29 in the 
nonfunctional calcium-binding site of cTnC. Interestingly, the mutation is 
located in a putative interaction site for the nonphosphorylated N-terminal arm 
of cardiac troponin I (cTnI) [ Finley NL, Abbott MB, Abusamhadneh E, Gaponenko 
V, Dong W, Seabrook G, Howarth JW, Rana M, Solaro RJ, Cheung HC et al. (1999) 
EJB Lett453, 107-112]. According to peptide array experiments, the 
nonphosphorylated cTnI arm interacts with cTnC around L29. This interaction is 
almost abolished by L29Q, as observed upon protein kinase A-dependent 
phosphorylation of cTnI at serine 22 and serine 23 in wild-type troponin. With 
CD spectroscopy, minor changes are observed in the backbone of Ca2+-free and 
Ca2+-saturated cTnC upon the L29Q replacement. A small, but significant, 
reduction in calcium sensitivity was detected upon measuring the Ca2+-dependent 
actomyosin subfragment 1 (actoS1)-ATPase activity and the sliding velocity of 
thin filaments. The maximum actoS1-ATPase activity, but not the maximum sliding 
velocity, was significantly enhanced. In addition, we performed our 
investigations at different levels of protein kinase A-dependent phosphorylation 
of cTnI. The in vitro assays mainly showed that the Ca2+ sensitivity of the 
actoS1-ATPase activity, and the mean sliding velocity of thin filaments, were no 
longer affected by protein kinase A-dependent phosphorylation of cTnI owing to 
the L29Q exchange in cTnC. The findings imply a hindered transduction of the 
phosphorylation signal from cTnI to cTnC.