131531 20240212170624.0 doi 10.1016/j.str.2019.03.016 sideral 111672 ART-2019-111672 eng Manso, José A. Integrin a6ß4 recognition of a linear motif of bullous pemphigoid antigen BP230 controls its recruitment to hemidesmosomes 2019 Access copy available to the general public Unrestricted 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 a6ß4 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 ß4. The crystal structure of the complex and mutagenesis analysis revealed that BP230 binds between the two domains of ß4. BP230 induces closing of the two FnIII domains that are locked in place by an interdomain ionic clasp required for binding. Disruption of BP230-ß4 binding prevents recruitment of BP230 to hemidesmosomes in human keratinocytes, revealing a key role of this interaction for hemidesmosome assembly. Phosphomimetic substitutions in ß4 and BP230 destabilize the complex. Thus, our study provides insights into the architecture of hemidesmosomes and potential mechanisms of regulation. info:eu-repo/grantAgreement/ES/DGA/E35-20R info:eu-repo/grantAgreement/EC/FP7/283570/EU/Transnational access and enhancement of integrated Biological Structure determination at synchrotron X-ray radiation facilities/BIOSTRUCT-X info:eu-repo/grantAgreement/ES/MEC/FPU14-06259 info:eu-repo/grantAgreement/ES/MINECO/BFU2009-08389 info:eu-repo/grantAgreement/ES/MINECO/BFU2015-69499-P info:eu-repo/grantAgreement/ES/MINECO/CTQ2015-64486-R info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 4.862 2019 BIOCHEMISTRY & MOLECULAR BIOLOGY 64 / 296 = 0.216 2019 Q1 T1 BIOPHYSICS 9 / 71 = 0.127 2019 Q1 T1 CELL BIOLOGY 61 / 194 = 0.314 2019 Q2 T1 2.786 2019 Structural Biology 2019 Q1 Molecular Biology 2019 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/submittedVersion Gómez-Hernández, María Carabias, Arturo Alonso-García, Noelia García-Rubio, Inés Universidad de Zaragoza (orcid)0000-0002-1827-1250 Kreft, Maaike Sonnenberg, Arnoud Pereda, José M. de 2003 395 Universidad de Zaragoza Dpto. Física Materia Condensa. Área Física Materia Condensada 27, 6 (2019), 952-964.e6 Structure Structure 0969-2126 5470484 http://zaguan.unizar.es/record/131531/files/texto_completo.pdf Preprint 2876867 http://zaguan.unizar.es/record/131531/files/texto_completo.jpg?subformat=icon icon Preprint oai:zaguan.unizar.es:131531 articulos driver 2024-02-12-17:05:34 ARTICLE