  Short-range interactions and long-range contacts drive the 3D folding of
structured proteins. The proteins' structure has a direct impact on their
biological function. However, nearly 40% of the eukaryotes proteome is composed
of intrinsically disordered proteins (IDPs) and protein regions that fluctuate
between ensembles of numerous conformations. Therefore, to understand their
biological function, it is critical to depict how the structural ensemble
statistics correlate to the IDPs' amino acid sequence. Here, using small-angle
x-ray scattering (SAXS) and time-resolved F\"orster resonance energy transfer
(trFRET), we study the intra-molecular structural heterogeneity of the
neurofilament low intrinsically disordered tail domain (NFLt). Using
theoretical results of polymer physics, we find that the Flory scaling exponent
of NFLt sub-segments correlates linearly with their net charge, ranging from
statistics of ideal to self-avoiding chains. Surprisingly, measuring the same
segments in the context of the whole NFLt protein, we find that regardless of
the peptide sequence, the segments' structural statistics are more expanded
than when measured independently. Our findings show that while polymer physics
can, to some level, relate the IDP's sequence to its ensemble conformations,
long-range contacts between distant amino acids play a crucial role in
determining intra-molecular structures. This emphasizes the necessity of
advanced polymer theories to fully describe IDPs ensembles with the hope it
will allow us to model their biological function.
