Journal Article PUBDB-2024-00891

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From isolated polyelectrolytes to star-like assemblies: the role of sequence heterogeneity on the statistical structure of the intrinsically disordered neurofilament-low tail domain

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2024
Springer Heidelberg

The European physical journal / E 47(2), 13 () [10.1140/epje/s10189-024-00409-8]
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Abstract: Intrinsically disordered proteins (IDPs) are a subset of proteins that lack stable secondary structure. Given their polymeric nature, previous mean-field approximations have been used to describe the statistical structure of IDPs. However, the amino-acid sequence heterogeneity and complex intermolecular interaction network have significantly impeded the ability to get proper approximations. One such case is the intrinsically disordered tail domain of neurofilament low (NFLt), which comprises a 50 residue-long uncharged domain followed by a 96 residue-long negatively charged domain. Here, we measure two NFLt variants to identify the impact of the NFLt two main subdomains on its complex interactions and statistical structure. Using synchrotron small-angle x-ray scattering, we find that the uncharged domain of the NFLt induces attractive interactions that cause it to self-assemble into star-like polymer brushes. On the other hand, when the uncharged domain is truncated, the remaining charged N-terminal domains remain isolated in solution with typical polyelectrolyte characteristics. We further discuss how competing long- and short-ranged interactions within the polymer brushes dominate their ensemble structure and, in turn, their implications on previously observed phenomena in NFL native and diseased states.

Classification:

Contributing Institute(s):
  1. EMBL-User (EMBL-User)
Research Program(s):
  1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)
Experiment(s):
  1. PETRA Beamline P12 (PETRA III)

Appears in the scientific report 2024
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Medline ; Creative Commons Attribution CC BY 4.0 ; OpenAccess ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2024-02-22, last modified 2025-07-23


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