Structural Heterogeneity in Intrinsically Disordered Proteins

  Sagi Meir  ,  Gil Rahamim  ,  Roy Beck  
The School of Physics and Astronomy, The Center for Nanoscience and Nanotechnology, and the Center for Physics and Chemistry of Living Systems, Tel Aviv University, Israel

Mean-field and scaling theories have been used repeatedly to describe many phenomena in physics. Specifically, Flory’s mean-field theory is used to describe the statistical mechanics of flexible homopolymers’ structures. Nonetheless, recent studies suggest that such mean-field approximation fails to describe heteropolymers such as intrinsically disordered proteins (IDP), where a complex interaction network may lead to structural heterogeneity. Using small-angle x-ray scattering and Forster resonance energy transfer measurements, we study the structural heterogeneity of the intrinsically disordered tail domain of the neurofilament-low protein (NFLt). By measuring the structures of the NFLt and the segments jointly composing this IDP, we directly demonstrated structural heterogeneity with alternative polymer statistics for the segments. Moreover, we found that the amino-acid context plays a critical role in determining the structure of NFLt. Our findings demonstrate that long- and short-ranged interactions within IDPs are required to explain the ensemble structural statistics in physiological conditions. This study further highlights IDPs’ unique characteristics in comparison to flexible homopolymers.