Latest publications

06 April 2020

  • The desmosome is a mesoscale lipid raft-like membrane domain.
    Related Articles

    The desmosome is a mesoscale lipid raft-like membrane domain.

    Mol Biol Cell. 2019 06 01;30(12):1390-1405

    Authors: Lewis JD, Caldara AL, Zimmer SE, Stahley SN, Seybold A, Strong NL, Frangakis AS, Levental I, Wahl JK, Mattheyses AL, Sasaki T, Nakabayashi K, Hata K, Matsubara Y, Ishida-Yamamoto A, Amagai M, Kubo A, Kowalczyk AP

    Desmogleins (Dsgs) are cadherin family adhesion molecules essential for epidermal integrity. Previous studies have shown that desmogleins associate with lipid rafts, but the significance of this association was not clear. Here, we report that the desmoglein transmembrane domain (TMD) is the primary determinant of raft association. Further, we identify a novel mutation in the DSG1 TMD (G562R) that causes severe dermatitis, multiple allergies, and metabolic wasting syndrome. Molecular modeling predicts that this G-to-R mutation shortens the DSG1 TMD, and experiments directly demonstrate that this mutation compromises both lipid raft association and desmosome incorporation. Finally, cryo-electron tomography indicates that the lipid bilayer within the desmosome is ∼10% thicker than adjacent regions of the plasma membrane. These findings suggest that differences in bilayer thickness influence the organization of adhesion molecules within the epithelial plasma membrane, with cadherin TMDs recruited to the desmosome via the establishment of a specialized mesoscale lipid raft-like membrane domain.

    PMID: 30943110 [PubMed - indexed for MEDLINE]

Selected publications

  • A flexible, multilayered protein scaffold maintains the slit in between glomerular podocytes.
    Grahammer F, Wigge C, Schell C, Kretz O, Patrakka J, Schneider S, Klose M, Arnold SJ, Habermann A, Bräuniger R, Rinschen MM, Völker L, Bregenzer A, Rubbenstroth D, Boerries M, Kerjaschki D, Miner JH, Walz G, Benzing T, Fornoni A, Frangakis AS, Huber TB. JCI Insight. 2016 Jun 16;1(9). pii: e86177.
    PubMed PMID: 27430022 


  • Helical arrays of U-shaped ATP synthase dimers form tubular cristae in ciliate mitochondria.
    Mühleip AW, Joos F, Wigge C, Frangakis AS, Kühlbrandt W, Davies KM.
    Proc Natl Acad Sci U S A. 2016 Jul 26;113(30):8442-7. doi: 10.1073/pnas.1525430113. Epub 2016 Jul 11.
    PubMed PMID: 27402755 


  • Three-dimensional CTF correction improves the resolution of electron tomograms.
    Kunz M, Frangakis AS.
    J Struct Biol. 2016 Jun 23. pii: S1047-8477(16)30122-8. doi: 10.1016/j.jsb.2016.06.016.
    PubMed PMID: 27343995 


        • M-free: Mask-independent scoring of the reference bias.
          Kunz M, Yu Z, Frangakis AS.
          J Struct Biol. 2015 Nov;192(2):307-11. doi: 10.1016/j.jsb.2015.08.016. Epub 2015 Aug 29.
          PubMed PMID: 26325584


  • Quantitative analysis of cytoskeletal reorganization during epithelial tissue sealing by large-volume electron tomography.
    Eltsov M, Dubé N, Yu Z, Pasakarnis L, Haselmann-Weiss U, Brunner D, Frangakis AS.
    Nat Cell Biol. 2015 May;17(5):605-14. doi: 10.1038/ncb3159. Epub 2015 Apr 20.
    PubMed PMID: 25893916


  • PLEKHM1 regulates Salmonella-containing vacuole biogenesis and infection.
    McEwan DG, Richter B, Claudi B, Wigge C, Wild P, Farhan H, McGourty K, Coxon FP, Franz-Wachtel M, Perdu B, Akutsu M, Habermann A, Kirchof A, Helfrich MH, Odgren PR, Van Hul W, Frangakis AS, Rajalingam K, Macek B, Holden DW, Bumann D, Dikic I.
    Cell Host Microbe. 2015 Jan 14;17(1):58-71. doi: 10.1016/j.chom.2014.11.011. Epub 2014 Dec 11.
    PubMed PMID: 25500191


  • Super-sampling SART with ordered subsets.
    Kunz M, Frangakis AS.
    J Struct Biol. 2014 Nov;188(2):107-15. doi: 10.1016/j.jsb.2014.09.010. Epub 2014 Oct 2.
    PubMed PMID: 25281496


  • M-free: scoring the reference bias in sub-tomogram averaging and template matching
    Yu Z, Frangakis AS.
    J Struct Biol. 2014 Jul;187(1):10-9. doi: 10.1016/j.jsb.2014.05.007. Epub 2014 May 22.
    PubMed PMID: 24859794


  • Correlative light- and electron microscopy with chemical tags.
    Perkovic M, Kunz M, Endesfelder U, Bunse S, Wigge C, Yu Z, Hodirnau VV, Scheffer MP, Seybert A, Malkusch S, Schuman J Struct Biol. 2014 May;186(2):205-13. doi: 10.1016/j.jsb.2014.03.018. Epub 2014 Mar 31.
    PubMed PMID: 24698954


  • CENP-A arrays are more condensed than canonical arrays at low ionic strength.
    Geiss CP, Keramisanou D, Sekulic N, Scheffer MP, Black BE, Frangakis AS.
    Biophys J. 2014 Feb 18;106(4):875-82. doi: 10.1016/j.bpj.2014.01.005.
    PubMed PMID: 24559990


  • Three-dimensional visualization of the molecular architecture of cell-cell junctions in situ by cryo-electron tomography of vitreous sections.
    Al-Amoudi A, Frangakis AS.
    Methods Mol Biol. 2013;961:97-117. doi: 10.1007/978-1-62703-227-8_4.
    PubMed PMID: 23325637


  • 3D Ultrastructural organization of whole Chlamydomonas reinhardtii cells studied by nanoscale soft x-ray tomography.
    Hummel E, Guttmann P, Werner S, Tarek B, Schneider G, Kunz M, Frangakis AS, Westermann B.
    PLoS One. 2012;7(12):e53293. doi: 10.1371/journal.pone.0053293. Epub 2012 Dec 31.
    PubMed PMID: 23300909


  • Heritable yeast prions have a highly organized three-dimensional architecture with interfiber structures.
    Saibil HR, Seybert A, Habermann A, Winkler J, Eltsov M, Perkovic M, Castaño-Diez D, Scheffer MP, Haselmann U, Chlanda P, Lindquist S, Tyedmers J, Frangakis AS.

    Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):14906-11. doi: 10.1073/pnas.1211976109. Epub 2012 Aug 27.
    PubMed PMID: 22927413


  • Room temperature L1₀ phase transformation in binary CoPt nanostructures prepared by focused-electron-beam-induced deposition.
    Porrati F, Begun E, Winhold M, Schwalb ChH, Sachser R, Frangakis AS, Huth M.
    Nanotechnology. 2012 May 11;23(18):185702. doi: 10.1088/0957-4484/23/18/185702. Epub 2012 Apr 13.
    PubMed PMID: 22499135


  • Human mitotic chromosomes consist predominantly of irregularly folded nucleosome fibres without a 30-nm chromatin structure.
    Nishino Y, Eltsov M, Joti Y, Ito K, Takata H, Takahashi Y, Hihara S, Frangakis AS, Imamoto N, Ishikawa T, Maeshima K.
    EMBO J. 2012 Apr 4;31(7):1644-53. doi: 10.1038/emboj.2012.35. Epub 2012 Feb 17.
    PubMed PMID: 22343941


  • Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs.
    Hergenreider E, Heydt S, Tréguer K, Boettger T, Horrevoets AJ, Zeiher AM, Scheffer MP, Frangakis AS, Yin X, Mayr M, Braun T, Urbich C, Boon RA, Dimmeler S.

    Nat Cell Biol. 2012 Feb 12;14(3):249-56. doi: 10.1038/ncb2441.
    PubMed PMID: 22327366


  • Nucleosomes stacked with aligned dyad axes are found in native compact chromatin in vitro.
    Scheffer MP, Eltsov M, Bednar J, Frangakis AS.

    J Struct Biol. 2012 May;178(2):207-14. doi: 10.1016/j.jsb.2011.11.020. Epub 2011 Nov 22.
    PubMed PMID: 22138167


  • Binary Pt-Si nanostructures prepared by focused electron-beam-induced deposition.
    Winhold M, Schwalb CH, Porrati F, Sachser R, Frangakis AS, Kämpken B, Terfort A, Auner N, Huth M.
    ACS Nano. 2011 Dec 27;5(12):9675-81. doi: 10.1021/nn203134a. Epub 2011 Nov 29.
    PubMed PMID: 22050515 


  • Evidence for short-range helical order in the 30-nm chromatin fibers of erythrocyte nuclei.
    Scheffer MP, Eltsov M, Frangakis AS.
    Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):16992-7. doi: 10.1073/pnas.1108268108. Epub 2011 Oct 3.
    PubMed PMID: 21969536


  • The three-dimensional molecular structure of the desmosomal plaque.
    Al-Amoudi A, Castaño-Diez D, Devos DP, Russell RB, Johnson GT, Frangakis AS.
    Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6480-5. doi: 10.1073/pnas.1019469108. Epub 2011 Apr 4.
    PubMed PMID: 21464301


  • Classification of electron sub-tomograms with neural networks and its application to template-matching.
    Yu Z, Frangakis AS.
    J Struct Biol. 2011 Jun;174(3):494-504. doi: 10.1016/j.jsb.2011.02.009. Epub 2011 Mar 5.
    PubMed PMID:21382496


  • Structure of reconstituted bacterial membrane efflux pump by cryo-electron tomography.
    Trépout S, Taveau JC, Benabdelhak H, Granier T, Ducruix A, Frangakis AS, Lambert O.Biochim Biophys Acta. 2010 Oct;1798(10):1953-60. doi: 10.1016/j.bbamem.2010.06.019. Epub 2010 Jul 1.
    PubMed PMID: 20599691


  • Visualization of macromolecular structures.
    O'Donoghue SI, Goodsell DS, Frangakis AS, Jossinet F, Laskowski RA, Nilges M, Saibil HR, Schafferhans A, Wade RC, Westhof E, Olson AJ.
    Nat Methods. 2010 Mar;7(3 Suppl):S42-55. doi: 10.1038/nmeth.1427. Epub 2010 Mar 1. Review.
    PubMed PMID: 20195256


  • Alignator: a GPU powered software package for robust fiducial-less alignment of cryo tilt-series.
    Castaño-Díez D, Scheffer M, Al-Amoudi A, Frangakis AS.
    J Struct Biol. 2010 Apr;170(1):117-26. doi: 10.1016/j.jsb.2010.01.014. Epub 2010 Feb 1
    PubMed PMID: 20117216


  • Quantitative and spatio-temporal features of protein aggregation in Escherichia coli and consequences on protein quality control and cellular ageing.
    Winkler J, Seybert A, König L, Pruggnaller S, Haselmann U, Sourjik V, Weiss M, Frangakis AS, Mogk A, Bukau B.
    EMBO J. 2010 Mar 3;29(5):910-23. doi: 10.1038/emboj.2009.412. Epub 2010 Jan 21.
    PubMed PMID: 20094032 


  • Proteome organization in a genome-reduced bacterium.
    Kühner S, van Noort V, Betts MJ, Leo-Macias A, Batisse C, Rode M, Yamada T, Maier T, Bader S, Beltran-Alvarez P, Castaño-Diez D, Chen WH, Devos D, Güell M, Norambuena T, Racke I, Rybin V, Schmidt A, Yus E, Aebersold R, Herrmann R, Böttcher B, Frangakis AS, Russell RB, Serrano L, Bork P, Gavin AC.
    Science. 2009 Nov 27;326(5957):1235-40. doi: 10.1126/science.1176343.
    PubMed PMID: 19965468


  • Cytoplasmic relaxation of active Eph controls ephrin shedding by ADAM10.
    Janes PW, Wimmer-Kleikamp SH, Frangakis AS, Treble K, Griesshaber B, Sabet O, Grabenbauer M, Ting AY, Saftig P, Bastiaens PI, Lackmann M.
    PLoS Biol. 2009 Oct;7(10):e1000215. doi: 10.1371/journal.pbio.1000215. Epub 2009 Oct 13.
    PubMed PMID: 19823572


  • Analysis of cryo-electron microscopy images does not support the existence of 30-nm chromatin fibers in mitotic chromosomes in situ.
    Eltsov M, Maclellan KM, Maeshima K, Frangakis AS, Dubochet J.
    Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19732-7. doi: 10.1073/pnas.0810057105. Epub 2008 Dec 8.
    PubMed PMID: 19064912


    • Performance evaluation of image processing algorithms on the GPU.
      Castaño-Díez D, Moser D, Schoenegger A, Pruggnaller S, Frangakis AS.
      J Struct Biol. 2008 Oct;164(1):153-60. doi: 10.1016/j.jsb.2008.07.006. Epub 2008 Jul 24.
      PubMed PMID: 18692140


  • A visualization and segmentation toolbox for electron microscopy.
    Pruggnaller S, Mayr M, Frangakis AS.
    J Struct Biol. 2008 Oct;164(1):161-5. doi: 10.1016/j.jsb.2008.05.003. Epub 2008 May 17.
    PubMed PMID: 18691905


  • Structural studies on desmosomes.
    Al-Amoudi A, Frangakis AS.
    Biochem Soc Trans. 2008 Apr;36(Pt 2):181-7. doi: 10.1042/BST0360181. Review.
    PubMed PMID: 18363559


  • Reprint of "Fiducial-less alignment of cryo-sections" [J. Struct. Biol. 159 (2007) 413-423].
    Castaño-Díez D, Al-Amoudi A, Glynn AM, Seybert A, Frangakis AS.
    J Struct Biol. 2008 Mar;161(3):249-59. doi: 10.1016/S1047-8477(08)00060-9.
    PubMed PMID: 18342740


  • The molecular architecture of cadherins in native epidermal desmosomes.
    Al-Amoudi A, Díez DC, Betts MJ, Frangakis AS.
    Nature. 2007 Dec 6;450(7171):832-7.
    PubMed PMID: 18064004


  • Classification of cryo-electron sub-tomograms using constrained correlation.
    Förster F, Pruggnaller S, Seybert A, Frangakis AS.
    J Struct Biol. 2008 Mar;161(3):276-86. Epub 2007 Jul 26.
    PubMed PMID: 17720536


  • Fiducial-less alignment of cryo-sections.
    Castaño-Díez D, Al-Amoudi A, Glynn AM, Seybert A, Frangakis AS
    J Struct Biol. 2007 Sep;159(3):413-23. Epub 2007 Jun 9.
    PubMed PMID: 17651988



  • Plastic-embedded protein crystals.
    Ravelli RB, Haselmann-Weiss U, McGeehan JE, McCarthy AA, Marquez JA, Antony C, Frangakis AS, Stranzl G.
    J Synchrotron Radiat. 2007 Jan;14(Pt 1):128-32. Epub 2006 Dec 15.
    PubMed PMID: 17211079


  • Visualization of cell microtubules in their native state.
    Bouchet-Marquis C, Zuber B, Glynn AM, Eltsov M, Grabenbauer M, Goldie KN, Thomas D, Frangakis AS, Dubochet J, Chrétien D.
    Biol Cell. 2007 Jan;99(1):45-53.
    PubMed PMID: 17049046


  • Implementation and performance evaluation of reconstruction algorithms on graphics processors.
    Castaño Díez D, Mueller H, Frangakis AS. 
    J Struct Biol. 2007 Jan;157(1):288-95. Epub 2006 Sep 1.
    PubMed PMID: 17029985


  • Multiple large filament bundles observed in Caulobacter crescentus by electron cryotomography.
    Briegel A, Dias DP, Li Z, Jensen RB, Frangakis AS, Jensen GJ.
    Mol Microbiol. 2006 Oct;62(1):5-14.
    PubMed PMID: 16987173


  • Structural analysis of Mycoplasma pneumoniae by cryo-electron tomography.
    Seybert A, Herrmann R, Frangakis AS.
    J Struct Biol. 2006 Nov;156(2):342-54. Epub 2006 May 7.
    PubMed PMID: 16875842


  • Tilt-series and electron microscope alignment for the correction of the non-perpendicularity of beam and tilt-axis.
    Díez DC, Seybert A, Frangakis AS.
    J Struct Biol. 2006 May;154(2):195-205. Epub 2006 Jan 26. 
    PubMed PMID: 16503168


  • Cryo-electron tomography reveals the cytoskeletal structure of Spiroplasma melliferum.
    Kürner J, Frangakis AS, Baumeister W.
    Science. 2005 Jan 21;307(5708):436-8.
    PubMed PMID: 15662018


  • Computational exploration of structural information from cryo-electron tomograms.
    Frangakis AS, Förster F.
    Curr Opin Struct Biol. 2004 Jun;14(3):325-31. Review.
    PubMed PMID: 15193312


  • Macromolecular architecture in eukaryotic cells visualized by cryoelectron tomography.
    Medalia O, Weber I, Frangakis AS, Nicastro D, Gerisch G, Baumeister W.
    Science. 2002 Nov 8;298(5596):1209-13.
    PubMed PMID: 112424373


  • Identification of macromolecular complexes in cryoelectron tomograms of phantom cells.
    Frangakis AS, Böhm J, Förster F, Nickell S, Nicastro D, Typke D, Hegerl R, Baumeister W.
    Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14153-8. Epub 2002 Oct 21.
    PubMed PMID: 12391313


  • Segmentation of two- and three-dimensional data from electron microscopy using eigenvector analysis.
    Frangakis AS, Hegerl R.
    J Struct Biol. 2002 Apr-May;138(1-2):105-13.
    PubMed PMID: 12160706


  • Noise reduction in electron tomographic reconstructions using nonlinear anisotropic diffusion.
    Frangakis AS, Hegerl R.
    J Struct Biol. 2001 Sep;135(3):239-50.
    PubMed PMID: 11722164


  • FhuA-mediated phage genome transfer into liposomes: a cryo-electron tomography study.
    Böhm J, Lambert O, Frangakis AS, Letellier L, Baumeister W, Rigaud JL.
    Curr Biol. 2001 Aug 7;11(15):1168-75.
    PubMed PMID: 11516947


  • Wavelet transform filtering and nonlinear anisotropic diffusion assessed for signal reconstruction performance on multidimensional biomedical data.
    Frangakis AS, Stoschek A, Hegerl R.
    IEEE Trans Biomed Eng. 2001 Feb;48(2):213-22.
    PubMed PMID: 11296877


  • Toward detecting and identifying macromolecules in a cellular context: template matching applied to electron tomograms.
    Bohm J, Frangakis AS, Hegerl R, Nickell S, Typke D, Baumeister W.
    Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14245-50.
    PubMed PMID: 11087814


  • Cryo-electron tomography of neurospora mitochondria.
    Nicastro D, Frangakis AS, Typke D, Baumeister W. 
    J Struct Biol. 2000 Feb;129(1):48-56.
    PubMed PMID: 10675296