Negative Charges at Protein Kinase C Sites of Troponin I Stabilize the Inactive State of Actin
Author
Mathur, Mohit C.; Kobayashi, Tomoyoshi; Chalovich, Joseph
Abstract
Alterations in the troponin complex can lead to increases or decreases in contractile activity. Most mutations of
troponin that cause hypertrophic cardiomyopathy increase the activity of cardiac muscle fibers. In at least some cases these
mutants stabilize the active state of regulated actin. In contrast, phosphorylation of troponin I at residues 43, 45, and 144 inhibits
muscle contractility. To determine if alterations of troponin I that reduce activity do stabilize the inactive state of actin, we
introduced negative charges at residues 43, 45, and 144 of troponin I to mimic a constitutively phosphorylated state. At saturating
calcium, all mutants decreased ATPase rates relative to wild-type actin-tropomyosin-troponin. Reduced activation of ATPase
activity was seen with a single mutation at S45E and was not further altered by mutating the other two sites. In the presence of low
concentrations of NEM-S1, wild-type troponin was more active than the mutants. At high NEM-S1, the rates of wild-type and
mutants approached the same limiting value. Changes in Ca21 affinity also support the idea that the equilibrium between states of
actin-tropomyosin-troponin was shifted to the inactive state by mutations that mimic troponin I phosphorylation. Originally published Biophysical Journal, Vol. 94, No. 2, Jan. 2008
Date
2008-01-15
Citation:
APA:
Mathur, Mohit C., & Kobayashi, Tomoyoshi, & Chalovich, Joseph. (January 2008).
Negative Charges at Protein Kinase C Sites of Troponin I Stabilize the Inactive State of Actin.
Biophysical Journal,
94(2),
542-
549. Retrieved from
http://hdl.handle.net/10342/3051
MLA:
Mathur, Mohit C., and Kobayashi, Tomoyoshi, and Chalovich, Joseph.
"Negative Charges at Protein Kinase C Sites of Troponin I Stabilize the Inactive State of Actin". Biophysical Journal.
94:2. (542-549),
January 2008.
September 26, 2023.
http://hdl.handle.net/10342/3051.
Chicago:
Mathur, Mohit C. and Kobayashi, Tomoyoshi and Chalovich, Joseph,
"Negative Charges at Protein Kinase C Sites of Troponin I Stabilize the Inactive State of Actin," Biophysical Journal 94, no.
2 (January 2008),
http://hdl.handle.net/10342/3051 (accessed
September 26, 2023).
AMA:
Mathur, Mohit C., Kobayashi, Tomoyoshi, Chalovich, Joseph.
Negative Charges at Protein Kinase C Sites of Troponin I Stabilize the Inactive State of Actin. Biophysical Journal.
January 2008;
94(2):
542-549.
http://hdl.handle.net/10342/3051. Accessed
September 26, 2023.
Collections
Publisher
East Carolina University