44963 20191105115757.0 doi 10.1107/S1399004715002485 sideral 90011 ART-2015-90011 eng Alonso-García, N. Combination of X-ray crystallography, SAXS and DEER to obtain the structure of the FnIII-3,4 domains of integrin a6b4 2015 Access copy available to the general public Unrestricted Integrin alpha6beta4 is a major component of hemidesmosomes that mediate the stable anchorage of epithelial cells to the underlying basement membrane. Integrin alpha6beta4 has also been implicated in cell proliferation and migration and in carcinoma progression. The third and fourth fibronectin type III domains (FnIII-3,4) of integrin beta4 mediate binding to the hemidesmosomal proteins BPAG1e and BPAG2, and participate in signalling. Here, it is demonstrated that X-ray crystallography, small-angle X-ray scattering and double electron– electron resonance (DEER) complement each other to solve the structure of the FnIII-3,4 region. The crystal structures of the individual FnIII-3 and FnIII-4 domains were solved and the relative arrangement of the FnIII domains was elucidated by combining DEER with site-directed spin labelling. Multiple structures of the interdomain linker were modelled by Monte Carlo methods complying with DEER constraints, and the final structures were selected against experimental scattering data. FnIII-3,4 has a compact and cambered flat structure with an evolutionary conserved surface that is likely to correspond to a protein-interaction site. Finally, this hybrid method is of general application for the study of other macromolecules and complexes. info:eu-repo/grantAgreement/ES/MINECO/BFU2009-08389 info:eu-repo/grantAgreement/ES/MINECO/BFU2012-32847 info:eu-repo/semantics/openAccess by-nc http://creativecommons.org/licenses/by-nc/3.0/es/ info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion (orcid)0000-0002-1827-1250 García-Rubio, I. Manso, J.A. Buey, R.M. Urien, H. Sonnenberg, A. Jeschke, G. de Pereda, J.M. D71 (2015), 969-985 Acta crystallogr., D Biol. crystallogr. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY 0907-4449 3294398 http://zaguan.unizar.es/record/44963/files/texto_completo.pdf Versión publicada 98592 http://zaguan.unizar.es/record/44963/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:44963 articulos driver 2019-11-05-11:49:14 ARTICLE