The delta-14 Mutation of Human Cardiac Troponin T Enhances ATPase Activity and Alters the Cooperative Binding of S1-ADP to Regulated Actin

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)
Bernhard Brenner (Creator)
Anmei Cai (Creator)
Joseph M. Chalovich (Creator)
P. Bryant Chase (Creator)
Scott Fredricksen (Creator)
Boris Gafurov (Creator)
Institution
East Carolina University (ECU )
Web Site: http://www.ecu.edu/lib/

Abstract: The complex of tropomyosin and troponin binds to actin and inhibits activation of myosin ATPase activity and force production of striated muscles at low free Ca2+ concentrations. Ca2+ stimulates ATP activity and at subsaturating actin concentrations the binding of NEM-modified S1 to actin– tropomyosin–troponin increases the rate of ATP hydrolysis even further. We show here that the ∆14 mutation of troponin T associated with familial hypertrophic cardiomyopathy results in an increase in ATPase rate like that seen with wild-type troponin in the presence of NEM-S1. The enhanced ATPase activity was not due to a decreased incorporation of mutant troponin T with roponin I and troponin C to form an active troponin complex. The activating effect was more prominent with a hybrid troponin (skeletal TnI TnC and cardiac TnT) than with all cardiac troponin. Thus it appears that changes in the troponin–troponin contacts that result from mutations or from forming hybrids stabilize a more active state of regulated actin. An analysis of the effect of the ∆14 mutation on the equilibrium binding of S1-ADP to actin was consistent with stabilization of an active state of actin. This change in activation may be important in the development of cardiac disease. Originally published Biochemistry Vol. 43 No. 48 Dec 2004

Additional Information

Publication
Other
Biochemistry. 43:48(December 2004) p. 15276-15285.
Language: English
Date: 2011
Keywords
S1-ADP, Tropomyosin, Troponin, actin

Email this document to

This item references:

TitleLocation & LinkType of Relationship
The delta-14 Mutation of Human Cardiac Troponin T Enhances ATPase Activity and Alters the Cooperative Binding of S1-ADP to Regulated Actinhttp://hdl.handle.net/10342/3287The described resource references, cites, or otherwise points to the related resource.