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Combination of X-ray crystallography, SAXS and DEER to obtain the structure of the FnIII-3,4 domains of integrin α6β4.

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Alonso-García N, García-Rubio I, Manso JA, Buey RM, Urien H, Sonnenberg A, Jeschke G, de Pereda JM
OpenAccess logo Acta Crystallogr D Biol Crystallogr 71 969-85 (2015)
Cited: 18 times
EuropePMC logo PMID: 25849406

Abstract

Integrin α6β4 is a major component of hemidesmosomes that mediate the stable anchorage of epithelial cells to the underlying basement membrane. Integrin α6β4 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 β4 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.

Articles - 4wtx mentioned but not cited (2)

  1. MMM: A toolbox for integrative structure modeling. Jeschke G. Protein Sci 27 76-85 (2018)
  2. Combination of X-ray crystallography, SAXS and DEER to obtain the structure of the FnIII-3,4 domains of integrin α6β4. Alonso-García N, García-Rubio I, Manso JA, Buey RM, Urien H, Sonnenberg A, Jeschke G, de Pereda JM. Acta Crystallogr D Biol Crystallogr 71 969-985 (2015)


Reviews citing this publication (2)

  1. The opposing roles of laminin-binding integrins in cancer. Ramovs V, Te Molder L, Sonnenberg A. Matrix Biol 57-58 213-243 (2017)
  2. Roles of Integrin α6β4 Glycosylation in Cancer. Kariya Y, Kariya Y, Gu J. Cancers (Basel) 9 E79 (2017)

Articles citing this publication (14)

  1. The contribution of modern EPR to structural biology. Jeschke G. Emerg Top Life Sci 2 9-18 (2018)
  2. Ensemble models of proteins and protein domains based on distance distribution restraints. Jeschke G. Proteins 84 544-560 (2016)
  3. Encoded loop-lanthanide-binding tags for long-range distance measurements in proteins by NMR and EPR spectroscopy. Barthelmes D, Gränz M, Barthelmes K, Allen KN, Imperiali B, Prisner T, Schwalbe H. J Biomol NMR 63 275-282 (2015)
  4. Spin labelling for integrative structure modelling: a case study of the polypyrimidine-tract binding protein 1 domains in complexes with short RNAs. Gmeiner C, Dorn G, Allain FHT, Jeschke G, Yulikov M. Phys Chem Chem Phys 19 28360-28380 (2017)
  5. Cross-validation of distance measurements in proteins by PELDOR/DEER and single-molecule FRET. Peter MF, Gebhardt C, Mächtel R, Muñoz GGM, Glaenzer J, Narducci A, Thomas GH, Cordes T, Hagelueken G. Nat Commun 13 4396 (2022)
  6. Inter-α-inhibitor heavy chain-1 has an integrin-like 3D structure mediating immune regulatory activities and matrix stabilization during ovulation. Briggs DC, Langford-Smith AWW, Birchenough HL, Jowitt TA, Kielty CM, Enghild JJ, Baldock C, Milner CM, Day AJ. J Biol Chem 295 5278-5291 (2020)
  7. Resolving distance variations by single-molecule FRET and EPR spectroscopy using rotamer libraries. Klose D, Holla A, Gmeiner C, Nettels D, Ritsch I, Bross N, Yulikov M, Allain FH, Schuler B, Jeschke G. Biophys J 120 4842-4858 (2021)
  8. EPR characterization of Mn(ii) complexes for distance determination with pulsed dipolar spectroscopy. Keller K, Zalibera M, Qi M, Koch V, Wegner J, Hintz H, Godt A, Jeschke G, Savitsky A, Yulikov M. Phys Chem Chem Phys 18 25120-25135 (2016)
  9. Modeling of the N-terminal Section and the Lumenal Loop of Trimeric Light Harvesting Complex II (LHCII) by Using EPR. Fehr N, Dietz C, Polyhach Y, von Hagens T, Jeschke G, Paulsen H. J Biol Chem 290 26007-26020 (2015)
  10. Reconstruction of Coupled Intra- and Interdomain Protein Motion from Nuclear and Electron Magnetic Resonance. Born A, Soetbeer J, Breitgoff F, Henen MA, Sgourakis N, Polyhach Y, Nichols PJ, Strotz D, Jeschke G, Vögeli B. J Am Chem Soc 143 16055-16067 (2021)
  11. Direct Binding of the Flexible C-Terminal Segment of Periaxin to β4 Integrin Suggests a Molecular Basis for CMT4F. Raasakka A, Linxweiler H, Brophy PJ, Sherman DL, Kursula P. Front Mol Neurosci 12 84 (2019)
  12. Characterization of Weak Protein Domain Structure by Spin-Label Distance Distributions. Ritsch I, Esteban-Hofer L, Lehmann E, Emmanouilidis L, Yulikov M, Allain FH, Jeschke G. Front Mol Biosci 8 636599 (2021)
  13. The Structure and Mechanism of Drug Transporters. Roberts AG. Methods Mol Biol 2342 193-234 (2021)
  14. EGFR-dependent tyrosine phosphorylation of integrin β4 is not required for downstream signaling events in cancer cell lines. Te Molder L, Kreft M, Heemskerk N, Schuring J, de Pereda JM, Wilhelmsen K, Sonnenberg A. Sci Rep 11 8675 (2021)


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