6GVK

Second pair of Fibronectin type III domains of integrin beta4 (T1663R mutant) bound to the bullous pemphigoid antigen BP230 (BPAG1e)

6GVK の概要

• エントリーDOI: 10.2210/pdb6gvk/pdb
• 関連するPDBエントリー: 6GVL
• 分子名称: Integrin beta-4, Dystonin, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: cytoskeleton, plakin, hemidesmosome, structural protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 26830.97

構造登録者

Manso, J.A.,Gomez-Hernandez, M.,Alonso-Garcia, N.,de Pereda, J.M. (登録日: 2018-06-21, 公開日: 2019-03-20, 最終更新日: 2024-10-23)

主引用文献

Manso, J.A.,Gomez-Hernandez, M.,Carabias, A.,Alonso-Garcia, N.,Garcia-Rubio, I.,Kreft, M.,Sonnenberg, A.,de Pereda, J.M.
Integrin alpha 6 beta 4 Recognition of a Linear Motif of Bullous Pemphigoid Antigen BP230 Controls Its Recruitment to Hemidesmosomes.
Structure, 27:952-, 2019

PubMed Abstract: Mechanical stability of epithelia requires firm attachment to the basement membrane via hemidesmosomes. Dysfunction of hemidesmosomal proteins causes severe skin-blistering diseases. Two plakins, plectin and BP230 (BPAG1e), link the integrin α6β4 to intermediate filaments in epidermal hemidesmosomes. Here, we show that a linear sequence within the isoform-specific N-terminal region of BP230 binds to the third and fourth FnIII domains of β4. The crystal structure of the complex and mutagenesis analysis revealed that BP230 binds between the two domains of β4. BP230 induces closing of the two FnIII domains that are locked in place by an interdomain ionic clasp required for binding. Disruption of BP230-β4 binding prevents recruitment of BP230 to hemidesmosomes in human keratinocytes, revealing a key role of this interaction for hemidesmosome assembly. Phosphomimetic substitutions in β4 and BP230 destabilize the complex. Thus, our study provides insights into the architecture of hemidesmosomes and potential mechanisms of regulation.

PubMed: 31006587
DOI: 10.1016/j.str.2019.03.016

実験手法

X-RAY DIFFRACTION (1.55 Å)