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Glioblastoma mutations modify EGFR dimer constitution to stop ligand bias


  • 1.

    Sharma, S. V., Bell, D. W., Settleman, J. & Haber, D. A. Epidermal expansion issue receptor mutations in lung most cancers. Nat. Rev. Most cancers 7, 169–181 (2007).

    CAS 
    PubMed 

    Google Scholar
     

  • 2.

    Brennan, C. W. et al. The somatic genomic panorama of glioblastoma. Mobile 155, 462–477 (2013).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 3.

    An, Z., Aksoy, O., Zheng, T., Fan, Q. W. & Weiss, W. A. Epidermal expansion issue receptor and EGFRvIII in glioblastoma: signaling pathways and centered treatments. Oncogene 37, 1561–1575 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 4.

    Wilson, Okay. J., Gilmore, J. L., Foley, J., Lemmon, M. A. & Riese, D. J., II. Purposeful selectivity of EGF circle of relatives peptide expansion elements: implications for most cancers. Pharmacol. Ther. 122, 1–8 (2009).

    CAS 
    PubMed 

    Google Scholar
     

  • 5.

    Freed, D. M. et al. EGFR ligands differentially stabilize receptor dimers to specify signaling kinetics. Mobile 171, 683–695 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 6.

    Macdonald-Obermann, J. L. & Pike, L. J. Other epidermal expansion issue (EGF) receptor ligands display distinct kinetics and biased or partial agonism for homodimer and heterodimer formation. J. Biol. Chem. 289, 26178–26188 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 7.

    Martínez-Jiménez, F. et al. A compendium of mutational most cancers driving force genes. Nat. Rev. Most cancers 20, 555–572 (2020).

    PubMed 

    Google Scholar
     

  • 8.

    Eck, M. J. & Yun, C. H. Structural and mechanistic underpinnings of the differential drug sensitivity of EGFR mutations in non-small mobile lung most cancers. Biochim. Biophys. Acta 1804, 559–566 (2010).

    CAS 
    PubMed 

    Google Scholar
     

  • 9.

    Tate, J. G. et al. COSMIC: {the catalogue} of somatic mutations in most cancers. Nucleic Acids Res. 47, D941–D947 (2019).

    CAS 
    PubMed 

    Google Scholar
     

  • 10.

    Heimberger, A. B. et al. Prognostic impact of epidermal expansion issue receptor and EGFRvIII in glioblastoma multiforme sufferers. Clin. Most cancers Res. 11, 1462–1466 (2005).

    CAS 
    PubMed 

    Google Scholar
     

  • 11.

    Eskilsson, E. et al. EGFR heterogeneity and implications for healing intervention in glioblastoma. Neuro Oncol. 20, 743–752 (2018).

    CAS 
    PubMed 

    Google Scholar
     

  • 12.

    Lee, J. C. et al. Epidermal expansion issue receptor activation in glioblastoma via novel missense mutations within the extracellular area. PLoS Med. 3, e485 (2006).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 13.

    Ng, P. Okay. et al. Systematic useful annotation of somatic mutations in most cancers. Most cancers Mobile 33, 450–462 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 14.

    Lu, C. et al. Structural proof for unfastened linkage between ligand binding and kinase activation within the epidermal expansion issue receptor. Mol. Mobile. Biol. 30, 5432–5443 (2010).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 15.

    Garrett, T. P. J. et al. Crystal constitution of a truncated epidermal expansion issue receptor extracellular area certain to reworking expansion issue alpha. Mobile 110, 763–773 (2002).

    CAS 
    PubMed 

    Google Scholar
     

  • 16.

    Ferguson, Okay. M. Construction-based view of epidermal expansion issue receptor law. Annu. Rev. Biophys. 37, 353–373 (2008).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 17.

    Ogiso, H. et al. Crystal constitution of the complicated of human epidermal expansion issue and receptor extracellular domain names. Mobile 110, 775–787 (2002).

    CAS 
    PubMed 

    Google Scholar
     

  • 18.

    Liebschner, D. et al. Polder maps: bettering OMIT maps by way of aside from bulk solvent. Acta Crystallogr. D Struct. Biol. 73, 148–157 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 19.

    Diwanji, D. et al. Constructions of the HER2–HER3–NRG1β complicated divulge a dynamic dimer interface. Nature 600, 339–343 (2021).

    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • 20.

    Alvarado, D., Klein, D. E. & Lemmon, M. A. Structural foundation for unfavorable cooperativity in expansion issue binding to an EGF receptor. Mobile 142, 568–579 (2010).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 21.

    Binder, Z. A. et al. Epidermal expansion issue receptor extracellular area mutations in glioblastoma provide alternatives for medical imaging and healing construction. Most cancers Mobile 34, 163–177 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 22.

    Orellana, L. et al. Oncogenic mutations on the EGFR ectodomain structurally converge to take away a steric hindrance on a kinase-coupled cryptic epitope. Proc. Natl Acad. Sci. USA 116, 10009–10018 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 23.

    Fan, Q. W. et al. EGFR phosphorylates tumor-derived EGFRvIII riding STAT3/5 and development in glioblastoma. Most cancers Mobile 24, 438–449 (2013).

    CAS 
    PubMed 

    Google Scholar
     

  • 24.

    An, Z. et al. EGFR cooperates with EGFRvIII to recruit macrophages in glioblastoma. Most cancers Res. 78, 6785–6794 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 25.

    Friedmann-Morvinski, D. et al. Dedifferentiation of neurons and astrocytes by way of oncogenes can induce gliomas in mice. Science 338, 1080–1084 (2012).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 26.

    Del Vecchio, C. A. et al. EGFRvIII gene rearrangement is an early tournament in glioblastoma tumorigenesis and expression defines a hierarchy modulated by way of epigenetic mechanisms. Oncogene 32, 2670–2681 (2013).

    MathSciNet 
    PubMed 

    Google Scholar
     

  • 27.

    Emlet, D. R. et al. Focused on a glioblastoma most cancers stem-cell inhabitants outlined by way of EGF receptor variant III. Most cancers Res. 74, 1238–1249 (2014).

    CAS 
    PubMed 

    Google Scholar
     

  • 28.

    Alcantara Llaguno, S. et al. Mobile-of-origin susceptibility to glioblastoma formation declines with neural lineage restriction. Nat. Neurosci. 22, 545–555 (2019).

    PubMed 

    Google Scholar
     

  • 29.

    Jaiswal, B. S. et al. Oncogenic ERBB3 mutations in human cancers. Most cancers Mobile 23, 603–617 (2013).

    CAS 
    PubMed 

    Google Scholar
     

  • 30.

    Hopkins, J. B., Gillilan, R. E. & Skou, S. BioXTAS RAW: enhancements to a unfastened open-source program for small-angle X-ray scattering knowledge relief and research. J. Appl. Cryst. 50, 1545–1553 (2017).

    CAS 

    Google Scholar
     

  • 31.

    Manalastas-Cantos, Okay. et al. ATSAS 3.0: expanded capability and new equipment for small-angle scattering knowledge research. J. Appl. Crystallogr. 54, 343–355 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 32.

    Lemmon, M. A. et al. Two EGF molecules give a contribution additively to stabilization of the EGFR dimer. EMBO J. 16, 281–294 (1997).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 33.

    Kabsch, W. XDS. Acta Crystallogr. D Biol. Crystallogr. 66, 125–132 (2010).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 34.

    CCP4. The CCP4 suite: systems for protein crystallography. Acta Crystallogr. D Biol. Crystallogr. 50, 760–763 (1994).


    Google Scholar
     

  • 35.

    McCoy, A. J. et al. Phaser crystallographic device. J. Appl. Cryst. 40, 658–674 (2007).

    CAS 

    Google Scholar
     

  • 36.

    Emsley, P. & Cowtan, Okay. Coot: model-building equipment for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126–2132 (2004).

    PubMed 

    Google Scholar
     

  • 37.

    Sensible, O. S. et al. Exploiting constitution similarity in refinement: automatic NCS and target-structure restraints in BUSTER. Acta Crystallogr. D Biol. Crystallogr. 68, 368–380 (2012).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 38.

    Adams, P. D. et al. PHENIX: a complete Python-based gadget for macromolecular constitution answer. Acta Crystallogr. D Biol. Crystallogr. 66, 213–221 (2010).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 39.

    Winn, M. D., Isupov, M. N. & Murshudov, G. N. Use of TLS parameters to mannequin anisotropic displacements in macromolecular refinement. Acta Crystallogr. D Biol. Crystallogr. 57, 122–133 (2001).

    CAS 
    PubMed 

    Google Scholar
     

  • 40.

    Chen, V. B. et al. MolProbity: all-atom constitution validation for macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr. 66, 12–21 (2010).

    CAS 
    PubMed 

    Google Scholar
     

  • 41.

    Dawson, J. P. et al. Epidermal expansion issue receptor dimerization and activation require ligand-induced conformational adjustments within the dimer interface. Mol. Mobile. Biol. 25, 7734–7742 (2005).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 42.

    Ferguson, Okay. M., Darling, P. J., Mohan, M. J., Macatee, T. L. & Lemmon, M. A. Extracellular domain names pressure homo- however now not hetero-dimerization of erbB receptors. EMBO J. 19, 4632–4643 (2000).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 43.

    Essletzbichler, P. et al. Megabase-scale deletion the usage of CRISPR/Cas9 to generate a completely haploid human mobile line. Genome Res. 24, 2059–2065 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 44.

    Kiyatkin, A., van Alderwerelt van Rosenburgh, I. Okay., Klein, D. E. & Lemmon, M. A. Kinetics of receptor tyrosine kinase activation outline ERK signaling dynamics. Sci. Sign. 13, eaaz5267 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 45.

    Aksamitiene, E., Hoek, J. B. & Kiyatkin, A. Multistrip western blotting: a device for comparative quantitative research of more than one proteins. Strategies Mol. Biol. 1312, 197–226 (2015).

    PubMed 

    Google Scholar
     

  • 46.

    Gao, J. et al. Integrative research of complicated most cancers genomics and medical profiles the usage of the cBioPortal. Sci. Sign. 6, pl1 (2013).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 47.

    Therneau, T. M. A bundle for survival research in R. https://CRAN.R-project.org/package=survival (2020).

  • 48.

    Kohsaka, S. et al. A technique of high-throughput useful analysis of EGFR gene variants of unknown importance in most cancers. Sci. Transl. Med. 9, eaan6566 (2017).

    PubMed 

    Google Scholar
     

  • 49.

    Neelam, B. et al. Construction–serve as research of ligand-induced epidermal expansion issue receptor dimerization. Biochemistry 37, 4884–4891 (1998).

    CAS 
    PubMed 

    Google Scholar
     

  • 50.

    Thompson, S. A., Harris, A., Hoang, D., Ferrer, M. & Johnson, G. R. COOH-terminal prolonged recombinant amphiregulin with bioactivity similar with naturally derived expansion issue. J. Biol. Chem. 271, 17927–17931 (1996).

    CAS 
    PubMed 

    Google Scholar
     

  • 51.

    Adam, R. et al. Modulation of the receptor binding affinity of amphiregulin by way of amendment of its carboxyl terminal tail. Biochim. Biophys. Acta 1266, 83–90 (1995).

    PubMed 

    Google Scholar
     

  • 52.

    Bessman, N. J., Bagchi, A., Ferguson, Okay. M. & Lemmon, M. A. Advanced courting between ligand binding and dimerization within the epidermal expansion issue receptor. Mobile Rep. 9, 1306–1317 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 53.

    Yu, S. et al. The non-small mobile lung most cancers EGFR extracellular area mutation, M277E, is oncogenic and drug-sensitive. Onco Objectives Ther. 10, 4507–4515 (2017).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 54.

    Liu, P. et al. A unmarried ligand is enough to turn on EGFR dimers. Proc. Natl Acad. Sci. USA 109, 10861–10866 (2012).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 55.

    Bessman, N. J., Freed, D. M. & Lemmon, M. A. Placing in combination buildings of epidermal expansion issue receptors. Curr. Opin. Struct. Biol. 29, 95–101 (2014).

    CAS 
    PubMed 

    Google Scholar
     

  • 56.

    Singh, B., Chippie, G. & Coffey, R. J. EGF receptor ligands: fresh advances. F1000Res. 5, 2270 (2016).


    Google Scholar
     

  • 57.

    Macdonald, J. L. & Pike, L. J. Heterogeneity in EGF-binding affinities arises from unfavorable cooperativity in an aggregating gadget. Proc. Natl Acad. Sci. USA 105, 112–117 (2008).

    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • 58.

    Ferguson, Okay. M., Hu, C. & Lemmon, M. A. Insulin and epidermal expansion issue receptor members of the family proportion parallel activation mechanisms. Protein Sci. 29, 1331–1344 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 59.

    Ferguson, Okay. M. et al. EGF turns on its receptor by way of taking out interactions that autoinhibit ectodomain dimerization. Mol. Mobile 11, 507–517 (2003).

    CAS 
    PubMed 

    Google Scholar
     

  • 60.

    Ramamurthy, V. et al. Constructions of adnectin/protein complexes divulge an expanded binding footprint. Construction 20, 259–269 (2012).

    CAS 
    PubMed 

    Google Scholar
     

  • 61.

    Matsuda, T. et al. Mobile-free synthesis of useful antibody fragments to supply a structural foundation for antibody-antigen interplay. PLoS ONE 13, e0193158 (2018).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 62.

    Li, S. et al. Structural foundation for inhibition of the epidermal expansion issue receptor by way of cetuximab. Most cancers Mobile 7, 301–311 (2005).

    CAS 
    PubMed 

    Google Scholar
     

  • 63.

    Lee, J. J. et al. Enzymatic prenylation and oxime ligation for the synthesis of strong and homogeneous protein–drug conjugates for centered remedy. Angew. Chem. Int. Ed. Engl. 54, 12020–12024 (2015).

    CAS 
    PubMed 

    Google Scholar
     

  • 64.

    Alvarado, D., Klein, D. E. & Lemmon, M. A. ErbB2 resembles an autoinhibited invertebrate epidermal expansion issue receptor. Nature 461, 287–291 (2009).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     


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