A small surface hydrophobic stripe in the coiled-coil domain of type I keratins mediates tetramer stability

Kelsie M. Bernot, Chang Hun Lee, Pierre A. Coulombe

Research output: Contribution to journalArticle

Abstract

Intermediate filaments (IFs) are fibrous polymers encoded by a large family of differentially expressed genes that provide crucial structural support in the cytoplasm and nucleus in higher eukaryotes. The mechanisms involved in bringing together ∼16 elongated coiled-coil dimers to form an IF are poorly defined. Available evidence suggests that tetramer subunits play a key role during IF assembly and regulation. Through molecular modeling and site-directed mutagenesis, we document a hitherto unnoticed hydrophobic stripe exposed at the surface of coiled-coil keratin heterodimers that contributes to the extraordinary stability of heterotetramers. The inability of K16 to form urea-stable tetramers in vitro correlates with an increase in its turnover rate in vivo. The data presented support a specific conformation for the assembly competent IF tetramer, provide a molecular basis for their differential stability in vitro, and point to the physiological relevance associated with this property in vivo.

Original languageEnglish (US)
Pages (from-to)965-974
Number of pages10
JournalJournal of Cell Biology
Volume168
Issue number6
DOIs
StatePublished - Mar 2005

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Type I Keratin
Intermediate Filaments
Keratins
Site-Directed Mutagenesis
Eukaryota
Urea
Polymers
Cytoplasm
Genes

ASJC Scopus subject areas

  • Cell Biology

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A small surface hydrophobic stripe in the coiled-coil domain of type I keratins mediates tetramer stability. / Bernot, Kelsie M.; Lee, Chang Hun; Coulombe, Pierre A.

In: Journal of Cell Biology, Vol. 168, No. 6, 03.2005, p. 965-974.

Research output: Contribution to journalArticle

Bernot, Kelsie M. ; Lee, Chang Hun ; Coulombe, Pierre A. / A small surface hydrophobic stripe in the coiled-coil domain of type I keratins mediates tetramer stability. In: Journal of Cell Biology. 2005 ; Vol. 168, No. 6. pp. 965-974.
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