Open AccessTransiently structured head domains control intermediate filament assembly
Author(s) -
Xiaoming Zhou,
YenChu Lin,
Masato Kato,
Eiichiro Mori,
Glen Liszczak,
Lillian B. Sutherland,
Vasiliy O. Sysoev,
Dylan T. Murray,
Robert Tycko,
Steven L. McKnight
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2022121118
Subject(s) - desmin , intermediate filament , protein filament , biophysics , chemistry , crystallography , stereochemistry , biology , biochemistry , cytoskeleton , cell , immunology , vimentin , immunohistochemistry
Significance Assembly of intermediate filaments (IFs) is reliant upon amino-terminal head domains. These head domains are of low sequence complexity and are assumed to function in the absence of structural order. Herein, we provide evidence that the head domains of the desmin and neurofilament light (NFL) IF proteins self-associate via the formation of labile but structurally specific cross-β interaction. Disease-causing mutations in the head domains of both proteins cause enhanced cross-β interactions. By assembling desmin and NFL IFs bearing isotopically labeled head domains, we provide evidence of structural order in properly assembled biological filaments. We propose that these observations on IF head domains may be instructive to the function of low complexity domains operative in other aspects of cell biology.