Structure-Function Analyses of a Keratin Heterotypic Complex Identify Specific Keratin Regions Involved in Intermediate Filament Assembly.
2B domain
crystal structure
cytoskeleton
epidermolysis bullosa simplex
epithelium
intermediate filament
keratinocyte
self-assembly
skin
structural protein
Journal
Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697
Informations de publication
Date de publication:
03 03 2020
03 03 2020
Historique:
received:
03
07
2019
revised:
20
10
2019
accepted:
07
01
2020
pubmed:
30
1
2020
medline:
30
4
2021
entrez:
30
1
2020
Statut:
ppublish
Résumé
Intermediate filaments (IFs) provide vital mechanical support in a broad array of cell types. Interference with this role causes cell fragility and accounts for a large number of human diseases. Gaining an understanding of the structure of IFs is paramount to understanding their function and designing therapeutic agents for relevant diseases. Here, we report the 2.6-Å resolution crystal structure of a complex of interacting 2B domains of keratin 5 (K5) and K14. K5 and K14 form a long-range, left-handed coiled coil, with participating α helices aligned in parallel and in register. Follow-up mutagenesis revealed that specific contacts between interacting 2B domains play a crucial role during 10-nm IF assembly, likely at the step of octamer-octamer association. The resulting structural model represents an atomic-resolution visualization of 2B-2B interactions important to filament assembly and provides insight into the defects introduced by mutations in IF genes associated with human skin diseases.
Identifiants
pubmed: 31995743
pii: S0969-2126(20)30002-2
doi: 10.1016/j.str.2020.01.002
pmc: PMC7058483
mid: NIHMS1554725
pii:
doi:
Substances chimiques
KRT14 protein, human
0
KRT5 protein, human
0
Keratin-14
0
Keratin-5
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
355-362.e4Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR042047
Pays : United States
Organisme : NIAMS NIH HHS
ID : R56 AR042047
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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