Disorder profile of nebulin encodes a vernier–like position sensor for the sliding thin and thick filaments of the skeletal muscle sarcomere
Ming-Chya Wu1,2*, Jeffrey G. Forbes3, Kuan Wang2,4
1Research Center for Adaptive Data Analysis, National Central University, Chungli, Taiwan
2Institute of Physics, Academia Sinica, Taipei, Taiwan
3TWIC, Inc, Maryland, USA
4Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
* presenting author:Ming-Chya Wu, email:mcwu@ncu.edu.tw
Nebulin is an about 1μm long intrinsically disordered scaffold for the thin filaments of skeletal muscle sarcomere. It is a multifunctional elastic protein that wraps around actin filament, stabilizes thin filaments and regulates Ca-dependent actomyosin interactions. This study investigates whether the disorder profile of nebulin might encode guidelines for thin and thick filament interactions in the sarcomere of the skeletal muscle. The question was addressed computationally by analyzing the predicted disorder probability of human nebulin (6669 residues, ~200 actin-binding repeats) by PONDR and the periodicity of the A-band stripes (reflecting the locations of myosin-associated proteins) in the electron micrographs of the sarcomere. Using the detrended fluctuation analysis, a scale factor for the A-band stripe image data with respect to the nebulin disorder probability was determined to make the thin and thick filaments aligned to have maximum correlation. The empirical mode decomposition method was then applied to identify hidden periodicities in both the nebulin disorder profile and the rescaled A-band data. The decomposition reveals three characteristic length scales (45nm, 100nm and 200nm) that are relevant for correlational analysis. The dynamical cross-correlation analyses with moving windows at various sarcomere lengths depict a vernier-like design for both periodicities, thus enabling nebulin to sense position and fine tune sarcomere overlap. This shows that the disorder profile of scaffolding proteins may encode a guideline for cellular architecture.

Keywords: Nebulin, Intrinsically disordered protein, Cross-correlation