Throughout my career I have used structural biology and biochemistry to understand the molecular basis of diseases caused by misbehaving enzymes in the human body. My rationale is that a thorough understanding on the molecular level of the disease-causing enzymes and their effects on cellular signalling pathways is essential for successful target identification and drug discovery.

I am particularly interested in the action of the E3 ubiquitin ligases, a vast and diverse family of more than 700 proteins in the human body. E3 ligases catalyse ubiquitination, one of the most diverse post-translational modifications that regulates nearly all processes inside a human cell.

In my lab, we utilise different techniques such as X-ray crystallography, cryo-EM, biochemistry, biophysics, cell biology and proteomics to comprehensively characterise E3 ligases from the molecular to the cellular level.


Selected publications from Dr Bernhard Lechtenberg

Wang XS*, Cotton TR*, Trevelyan SJ, Richardson LW, Lee WT, Silke J, Lechtenberg BC. The unifying catalytic mechanism of the RING-between-RING E3 ubiquitin ligase family. Nature Communications. 2023;14(1):168. PMID: 36631489

Cotton TR, Cobbold SA, Bernardini JP, Richardson LW, Wang XS, Lechtenberg BC. Structural basis of K63-ubiquitin chain formation by the Gordon-Holmes syndrome RBR E3 ubiquitin ligase RNF216. Molecular Cell. 2022;82(3):598-615. PMID: 34998453

Lechtenberg BC, Gehring MP, Light TP, Horne CR, Matsumoto MW, Hristova K, Pasquale EB. Regulation of the EphA2 receptor intracellular region by phosphomimetic negative charges in the kinase-SAM linker. Nature Communications. 2021;12(1):7047. PMID: 34857764

Klemm T, Ebert G, Calleja DJ, Allison CC, Richardson LW, Bernardini JP, Lu BG, Kuchel NW, Grohmann C, Shibata Y, Gan ZY, Cooney JP, Doerflinger M, Au AE, Blackmore TR, van der Heden van Noort GJ, Geurink PP, Ovaa H, Newman J, Riboldi-Tunnicliffe A, Czabotar PE, Mitchell JP, Feltham R, Lechtenberg BC, Lowes KN, Dewson G, Pellegrini M, Lessene G, Komander D. Mechanism and inhibition of the papain-like protease, PLpro, of SARS-CoV-2. The EMBO Journal. 2020;39(18):e106275. PMID: 32845033

Cotton TR, Lechtenberg BC. Chain reactions: molecular mechanisms of RBR ubiquitin ligases. Biochem Soc Trans. 2020;48(4):1737-50. PMID: 32677670

Shin K*, Lechtenberg BC*, Fujimoto LM, Yao Y, Bartra SS, Plano GV, Marassi FM. Structure of human Vitronectin C-terminal domain and interaction with Yersinia pestis outer membrane protein Ail. Science Advances. 2019;5(9):eaax5068. PMID: 31535027

Lechtenberg BC, Rajput A, Sanishvili R, Dobaczewska MK, Ware CF, Mace PD, Riedl SJ. Structure of a HOIP/E2~ubiquitin complex reveals RBR E3 ligase mechanism and regulation. Nature. 2016;529(7587):546-50. PMID: 26789245

Lamberto I*, Lechtenberg BC*, Olson EJ*, Mace PD, Dawson PE, Riedl SJ, Pasquale EB. Development and structural analysis of a nanomolar cyclic peptide antagonist for the EphA4 receptor. ACS Chem Biol. 2014;9(12):2787-95. PMID: 25268696

Lechtenberg BC*, Murray-Rust TA*, Johnson DJ, Adams TE, Krishnaswamy S, Camire RM, Huntington JA. Crystal structure of the prothrombinase complex from the venom of Pseudonaja textilis. Blood. 2013;122(16):2777-83. PMID: 23869089

Lechtenberg BC, Johnson DJ, Freund SM, Huntington JA. NMR resonance assignments of thrombin reveal the conformational and dynamic effects of ligation. PNAS. 2010;107(32):14087-92. PMID: 20660315

Lab research projects

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