Interaction of MyBP-C with Thin Filaments

Recent in vitro studies have shown that the binding of MyBP-C to thin filaments affects sliding velocity and troponin-tropomyosin-based regulation. We have therefore been investigating the detailed nature of this binding by negative staining and 3D image reconstruction (in collaboration with Drs. J. Robbins and W. Lehman). N-terminal fragments of MyBP-C decorate actin in a regular way. Reconstructions show that the molecule runs tangentially along the filament (left image), with its actin-bound end probably competing with tropomyosin for actin binding in the low Ca2+ position (middle image) but probably not in the high Ca2+ position (right). These results provide structural insights into MyBP-C’s influence on contraction (Mun et al., 2011).

Left: 3D reconstruction of F-actin (grey) decorated with N-terminal fragment of MyBP-C (beige). Approximate atomic fit of MyBP-C domains shows how density can be accounted for. Middle and right: same fit, but showing how MyBP-C could influence tropomyosin position in low Ca2+ state (middle) compared with little effect in high Ca2+ state (right). See Mun et al., 2011.