Dynamic Protein Interactions

  • Rejnowicz E, Batchelor M, Leen E, Ahangar MS, Burgess SG, Richards MW, Kalverda AP, Bayliss R (2024) Exploring the dynamics and interactions of the N-myc transactivation domain through solution nuclear magnetic resonance spectroscopy. Biochem J. 481(21):1535-1556. https://doi.org/10.1042/BCJ20240248
  • Bayliss R, Burgess SG, Leen E, Richards MW (2017) A moving target: structure and disorder in pursuit of Myc inhibitors. Biochem Soc Trans. 45(3):709-717. https://doi.org/10.1042/BST20160328 (Review)
  • Richards MW, Burgess SG, Poon E, Carstensen A, Eilers M, Chesler L, Bayliss R (2016) Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors. Proc. Natl. Acad. Sci. USA.113:13726-13731. https://doi.org/10.1073/pnas.1610626113

Protein Kinases and Cancer Drug Discovery

  • Arter C, Trask L, Ward S, Yeoh S, Bayliss R (2022) Structural features of the protein kinase domain and targeted binding by small-molecule inhibitors. J Biol Chem. 298(8):102247. https://doi.org/10.1016/j.jbc.2022.102247
  • Batchelor M, Dawber RS, Wilson AJ, Bayliss R. (2022) α-Helix stabilization by co-operative side chain charge-reinforced interactions to phosphoserine in a basic kinase-substrate motif Biochem J 479(5):687-700. https://doi.org/10.1042/BCJ20200128
  • Kakade P, Ojha H, Raimi OG, Shaw A, Waddell AD, Ault JR, Burel S, Brockmann K, Kumar A, Ahangar MS, Krysztofinska EM, Macartney T, Bayliss R, Fitzgerald JC, Muqit MMK (2021) Mapping of a N-terminal α-helix domain required for human PINK1 stabilisation, Serine228 autophosphorylation and activation in cells. Open Biol. 12(1):210264. https://doi.org/10.1098/rsob.210264
  • Tomlinson LJ, Batchelor M, Byrne DP, Sarsby J, Brownridge PJ, Bayliss R, Eyers PA, Eyers CE (2021) Exploring the conformational landscape and stability of Aurora A using ion-mobility mass spectrometry and molecular modelling. J Am Soc Mass Spectrom. https://doi.org/10.1021/jasms.1c00271
  • Byrne MJ, Nasir N, Basmadjian C, Bhatia C, Cunnison RF, Carr KH, Mas-Droux C, Yeoh S, Cano C, Bayliss R (2020) Nek7 conformational flexibility and inhibitor binding probed through protein engineering of the R-spine Biochem J 477(8):1525–1539. https://doi.org/10.1042/bcj20210812
  • Zhang R, McIntyre PJ, Collins PM, Foley DJ, Arter C, von Delft F, Bayliss R, Warriner S, Nelson A (2019) Construction of a Shape-Diverse Fragment Set: Design, Synthesis and Screen against Aurora-A Kinase. Chemistry – A European Journal 25(27):6831-6839. https://doi.org/10.1002/chem.201900815
  • McIntyre PJ, Collins PM, Vrzal L, Birchall K, Arnold LH, Mpamhanga C, Coombs PJ, Burgess SG, Richards MW, Winter A, Veverka V, Delft FV, Merritt A, Bayliss R (2017). Characterization of Three Druggable Hot-Spots in the Aurora-A/TPX2 Interaction Using Biochemical, Biophysical, and Fragment-Based Approaches. ACS Chem. Biol. 12(11): 2906–2914 https://doi.org/10.1021/acschembio.7b00537
  • Coxon CR, Wong C, Bayliss R, Boxall K, Carr KH, Fry AM, Hardcastle IR, Matheson CJ, Newell DR, Sivaprakasam M, Thomas H, Turner D, Yeoh S, Wang LZ, Griffin RJ, Golding BT, Cano C. (2017) Structure-guided design of purine-based probes for selective Nek2 inhibition. Oncotarget 8(12):19089-19124. https://doi.org/10.18632/oncotarget.13249
  • Burgess SG, Oleksy A, Cavazza T, Richards MW, Vernos I, Matthews D, Bayliss R (2016) Allosteric inhibition of Aurora-A kinase by a synthetic vNAR domain. Open Biol. 6:160089. https://doi.org/10.1098/rsob.160089
  • Rennie YK, McIntyre PJ, Akindele T, Bayliss R, Jamieson AG (2016)A TPX2 Proteomimetic Has Enhanced Affinity for Aurora-A Due to Hydrocarbon Stapling of a Helix. ACS Chem. Biol. 11(12):3383-3390. https://doi.org/10.1021/acschembio.6b00727
  • Rogerson D, Sachdeva A, Wang K, Haq T, Kazlauskaite A, Muqit MMK, Fry AM, Bayliss R, Chin J (2015) Efficient and site-specific incorporation of phosphoserine and its non-hydrolyzable analog. Nat. Chem. Biol.11:496-503. https://doi.org/10.1038/nchembio.1823

Cancer Signalling Pathways

  • Vidal R, Leen E, Herold S, Müller M, Fleischhauer D, Schülein-Völk C, Papadopoulos D, Röschert I, Uhl L, Ade CP, Gallant P, Bayliss R, Eilers M, Büchel G (2024) Association with TFIIIC limits MYCN localisation in hubs of active promoters and chromatin accumulation of non-phosphorylated RNA polymerase II. Elife 13:RP94407 https://doi.org/10.7554/eLife.94407.3
  • Sampson J, Ju HM, Song JY, Fry AM, Bayliss R, Choi J (2022) A Polytherapy Strategy Using Vincristine and ALK Inhibitors to Sensitise EML4-ALK-Positive NSCLC. Cancers (Basel) 14(3):779. https://doi.org/10.3390/cancers14030779
  • Roeschert I, Poon E, Henssen AG, Dorado Garcia H, Gatti M, Giansanti C, Jamin Y, Ade CP, Gallant P, Schülein-Völk C, Beli P, Richards MW, Rosenfeldt M, Altmeyer M, Anderson J, Eggert A, Dobbelstein M, Bayliss R, Chesler L, Büchel G, Eilers M. (2021) Combined inhibition of Aurora-A and ATR kinases results in regression of MYCN-amplified neuroblastoma. Nature Cancer 2(3):312-326. https://doi.org/10.1038/s43018-020-00171-8
  • Sampson J, Richards MW, Choi J, Fry AM, Bayliss R (2021) Phase‐separated foci of EML4‐ALK facilitate signalling and depend upon an active kinase conformation. EMBO Reports 22(12) pii: e53693 https://doi.org/10.15252/embr.202153693
  • O’Regan L, Barone G, Adib R, Woo CG, Jeong HJ, Richardson EL, Richards MW, Muller PAJ, Collis SJ, Fennell DA, Choi J, Bayliss R, Fry AM (2020) EML4–ALK V3 oncogenic fusion proteins promote microtubule stabilization and accelerated migration through NEK9 and NEK7. J Cell Sci. 133(9) pii: jcs241505. https://doi.org/10.1242/jcs.241505
  • Sabir SR, Yeoh S, Jackson G, Bayliss R (2017) EML4-ALK Variants: Biological and Molecular Properties, and the Implications for Patients. Cancers  9(9). pii: E118. https://doi.org/10.3390/cancers9090118 (Review)
  • Woo CG, Seo S, Kim SW, Jang SJ, Park KS, Song JY, Lee B, Richards MW, Bayliss R, Lee DH, Choi J (2017) Differential protein stability and clinical responses of EML4-ALK fusion variants to various ALK inhibitors in advanced ALK-rearranged non-small cell lung cancer. Ann Oncol. 28(4):791-797. https://doi.org/10.1093/annonc/mdw693
  • Richards MW, Law EP, Rennalls LP, Busacca S, O’Regan L, Fry AM, Fennell DA, Bayliss R (2014) Crystal structure of EML1 reveals the basis for Hsp90 dependence of oncogenic EML4-ALK by disruption of an atypical b-propeller domain. Proc. Natl. Acad. Sci. USA 111:5195-200. https://doi.org/10.1073/pnas.1322892111
  • Joshi A, Newbatt Y, McAndrew PC, Stubbs M, Burke R, Richards MW, Caldwell JJ, McHardy T, Collins I, Bayliss R (2015) Molecular mechanisms of human IRE1 activation through dimerization and ligand binding. Oncotarget 6(15):13019-35. https://doi.org/10.18632/oncotarget.3864

Cell Division

  • Holder J, Miles JA, Batchelor M, Popple H, Walko M, Yeung W, Kannan N, Wilson AJ, Bayliss R, Gergely F (2024) CEP192 localises mitotic Aurora-A activity by priming its interaction with TPX2. EMBO J. https://doi.org/10.1038/s44318-024-00240-z Online ahead of print. PMID: 39327527
  • Ryan EL, Shelford J, Massam-Wu T, Bayliss R, Royle SJ (2021) Defining endogenous TACC3–chTOG–clathrin–GTSE1 interactions at the mitotic spindle using induced relocalization. J Cell Sci. 134(3). pii: jcs255794. https://doi.org/10.1242/jcs.255794
  • Adib R, Montgomery JM, Atherton J, O’Regan L, Richards MW, Straatman KR, Roth D, Straube A, Bayliss R, Moores CA, Fry AM (2019) Mitotic phosphorylation by NEK6 and NEK7 reduces the microtubule affinity of EML4 to promote chromosome congression Sci. Signaling 12(594) pii:eaaw2939 https://doi.org/10.1126/scisignal.aaw2939
  • Burgess SG, Mukherjee M, Sabir S, Joseph N, Gutiérrez-Caballero C, Richards MW, Huguenin-Dezot N, Chin JW, Kennedy EJ, Pfuhl M, Royle SJ, Gergely F, Bayliss R. (2018) Mitotic spindle association of TACC3 requires Aurora-A-dependent stabilization of a cryptic α-helix. EMBO J. 37(8). pii: e97902. https://doi.org/10.15252/embj.201797902
  • Büchel G, Carstensen A, Mak KY, Roeschert I, Leen E, Sumara O, Hofstetter J, Herold S, Kalb J, Baluapuri A, Poon E, Kwok C, Chesler L, Maric HM, Rickman DS, Wolf E, Bayliss R, Walz S, Eilers M. (2017) Association with Aurora-A Controls N-MYC-Dependent Promoter Escape and Pause Release of RNA Polymerase II during the Cell Cycle. Cell Rep. 21:3483-3497. https://doi.org/10.1016/j.celrep.2017.11.090
  • Bachmann G,  Richards MW, Winter A, Beuron F, Morris E, Bayliss R (2016) A closed conformation of the C. elegans separase-securin complex. Open Biol. 6: 160032.
  • Haq T, Richards MW, Burgess SG, Gallego P, Yeoh S, O’Regan L, Reverter D, Roig J, Fry AM, Bayliss R(2015) Mechanistic basis of Nek7 activation through Nek9 binding and induced dimerization. Nat Commun. 6:8771. https://doi.org/10.1038/ncomms9771