puc-header

Integrin α6β4 Recognition of a Linear Motif of Bullous Pemphigoid Antigen BP230 Controls Its Recruitment to Hemidesmosomes

53 Pages Posted: 7 Feb 2019 Sneak Peek Status: Under Review

See all articles by José A Manso

José A Manso

University of Salamanca - Institute of Molecular and Cellular Cancer Biology- Instituto de Biología Molecular y Celular del Cáncer

María Gómez-Hernández

University of Salamanca - Institute of Molecular and Cellular Cancer Biology- Instituto de Biología Molecular y Celular del Cáncer

Arturo Carabias

University of Salamanca - Institute of Molecular and Cellular Cancer Biology- Instituto de Biología Molecular y Celular del Cáncer

Noelia Alonso-García

University of Salamanca - Institute of Molecular and Cellular Cancer Biology- Instituto de Biología Molecular y Celular del Cáncer

Inés García-Rubio

Centro Universitario de la Defensa de Zaragoza

Maaike Kreft

The Netherlands Cancer Institute

Arnoud Sonnenberg

The Netherlands Cancer Institute

Jose M. de Pereda

University of Salamanca - Institute of Molecular and Cellular Cancer Biology- Instituto de Biología Molecular y Celular del Cáncer

More...

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 looked in place by an inter-domain ionic clasp required for binding. Disruption of the BP230-β4 interface prevents the recruitment of BP230 to hemidesmosomes in human keratinocytes, revealing a key role of the BP230-β4 interaction for hemidesmosome assembly. Our study provides insights into the molecular mechanisms of hemidesmosome architecture and regulation.

Keywords: Cell adhesion, Epithelia, Keratinocytes, Plakins, Protein-protein interactions

Suggested Citation

Manso, José A and Gómez-Hernández, María and Carabias, Arturo and Alonso-García, Noelia and García-Rubio, Inés and Kreft, Maaike and Sonnenberg, Arnoud and de Pereda, Jose M., Integrin α6β4 Recognition of a Linear Motif of Bullous Pemphigoid Antigen BP230 Controls Its Recruitment to Hemidesmosomes (February 7, 2019). Available at SSRN: https://ssrn.com/abstract=3330561 or http://dx.doi.org/10.2139/ssrn.3330561
This is a paper under consideration at Cell Press and has not been peer-reviewed.

José A Manso

University of Salamanca - Institute of Molecular and Cellular Cancer Biology- Instituto de Biología Molecular y Celular del Cáncer

Salamanca, 37007
Spain

María Gómez-Hernández

University of Salamanca - Institute of Molecular and Cellular Cancer Biology- Instituto de Biología Molecular y Celular del Cáncer

Salamanca, 37007
Spain

Arturo Carabias

University of Salamanca - Institute of Molecular and Cellular Cancer Biology- Instituto de Biología Molecular y Celular del Cáncer

Salamanca, 37007
Spain

Noelia Alonso-García

University of Salamanca - Institute of Molecular and Cellular Cancer Biology- Instituto de Biología Molecular y Celular del Cáncer

Salamanca, 37007
Spain

Inés García-Rubio

Centro Universitario de la Defensa de Zaragoza

Academia General Militar, Ctra. de Huesca, s/n
Zaragoza, Zaragoza 50009
Spain

Maaike Kreft

The Netherlands Cancer Institute

Plesmanlaan 121
Amsterdam, 1066 CX
Netherlands

Arnoud Sonnenberg

The Netherlands Cancer Institute

Plesmanlaan 121
Amsterdam, 1066 CX
Netherlands

Jose M. De Pereda (Contact Author)

University of Salamanca - Institute of Molecular and Cellular Cancer Biology- Instituto de Biología Molecular y Celular del Cáncer ( email )

Salamanca, 37007
Spain