4QMD

Crystal structure of human envoplakin plakin repeat domain

4QMD の概要

• エントリーDOI: 10.2210/pdb4qmd/pdb
• 分子名称: Envoplakin (2 entities in total)
• 機能のキーワード: envoplakin, periplakin, plakin protein, plakin repeat domain, cornified envelope, epidermal permeability barrier, keratinocyte, terminal differentiation, intermediate filament, vimentin, cytoskeleton, cell junction, desmosome, paraneoplastic pemphigus, cell adhesion
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell junction, desmosome: Q92817
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 42480.75

構造登録者

Mohammed, F.,Al-Jassar, C.,White, S.A.,Fogl, C.,Jeeves, M.,Knowles, T.J.,Odinstova, E.,Rodriguez-Zamora, P.,Overduin, M.,Chidgey, M. (登録日: 2014-06-16, 公開日: 2015-07-29, 最終更新日: 2024-02-28)

主引用文献

Fogl, C.,Mohammed, F.,Al-Jassar, C.,Jeeves, M.,Knowles, T.J.,Rodriguez-Zamora, P.,White, S.A.,Odintsova, E.,Overduin, M.,Chidgey, M.
Mechanism of intermediate filament recognition by plakin repeat domains revealed by envoplakin targeting of vimentin.
Nat Commun, 7:10827-10827, 2016

PubMed Abstract: Plakin proteins form critical connections between cell junctions and the cytoskeleton; their disruption within epithelial and cardiac muscle cells cause skin-blistering diseases and cardiomyopathies. Envoplakin has a single plakin repeat domain (PRD) which recognizes intermediate filaments through an unresolved mechanism. Herein we report the crystal structure of envoplakin's complete PRD fold, revealing binding determinants within its electropositive binding groove. Four of its five internal repeats recognize negatively charged patches within vimentin via five basic determinants that are identified by nuclear magnetic resonance spectroscopy. Mutations of the Lys1901 or Arg1914 binding determinants delocalize heterodimeric envoplakin from intracellular vimentin and keratin filaments in cultured cells. Recognition of vimentin is abolished when its residues Asp112 or Asp119 are mutated. The latter slot intermediate filament rods into basic PRD domain grooves through electrosteric complementarity in a widely applicable mechanism. Together this reveals how plakin family members form dynamic linkages with cytoskeletal frameworks.

PubMed: 26935805
DOI: 10.1038/ncomms10827

実験手法

X-RAY DIFFRACTION (1.601 Å)