posters 5th Asia-Pacific NMR Symposium 2013

A combined NMR, small-angle X-ray and neutron scattering approach reveals structural flexibility, the modular architecture and modes of action of the cardiac myosin binding protein C (#157)

Ann Kwan 1 , Yanling Lu 1 , Cy Jeffries 1 , Kate Michie 1 , Mitchell Guss 1 , Jill Trewhella 1
  1. University of Sydney, Sydney, NSW, Australia

The N-terminal domains of cardiac myosin binding protein C (MyBP-C) have been known to play a number of regulatory roles during heart muscle contraction by modulating interactions with myosin and actin, two essential proteins involved in cell motility and muscle contractions. We have used a combined NMR, small-angle X-ray scattering and neutron scattering (SAXS and SANS, respectively) approach to determine the modular organization and flexibility of the N-terminal domains. In addition, using NMR and fluorescence titration studies, we have identified the specific regions on cMyBP-C that are responsible for its interaction with actin as well as with the ubiquitous and multi-functional calcium sensor calmodulin (CaM). Interestingly, the actin-interaction "hot-spots" of cMyBP-C overlap with previously identified myosin-binding sites while the binding to CaM is mediated via the hydrophobic clefts within both lobes of the CaM dumbbell structure sensitive to calcium binding. The implications of these findings in the biological context will be discussed. Our results highlight how NMR together with SAXS and SANS can reveal important biological insights about large and dynamic protein complexes.