Anne Conibear
Assistant Professor, TU Wien
Posttranslational Modifications of Disordered Proteins
Abstract
The conformational flexibility of intrinsically disordered proteins and protein regions (IDRs), and their accessibility to modifying enzymes make IDRs hot-spots for protein regulation by posttranslational modifications (PTMs). Such PTMs increase the complexity of the proteome and can have central roles in regulating protein function, location, interactions and degradation. Little is known, however, about how PTMs modulate the conformations and interactions of IDRs, as they typically occupy multiple conformational states, have promiscuous interactions, and are often removed or poorly represented in structural biology studies. In this presentation, I will discuss our work towards understanding how PTMs modulate the conformations and interactions of IDRs. Protein synthesis and semi-synthesis provides access to site-specifically modified variants of IDRs, such as the HMGN1 and Tau proteins, and disordered termini of Hsp90 and β-catenin. These protein variants enable us to study the precise effects of PTMs and cross-talk of multiple PTMs on conformational populations using NMR spectroscopy. With these examples, I aim to show how integrating chemical protein synthesis with structural biology of IDRs allows us to gain new insights into the effects of PTMs on the conformation, dynamics and regulation of IDRs.
References:
[1] Conibear, A. C., Nat. Rev. Chem. 4, 674-695 (2020).
[2] Niederacher, G., Urwin, D.; Dijkwel, Y., Tremethick, D. J., Rosengren, K. J., Becker, C. F. W., Conibear, A. C., RSC Chem. Biol. 2, 537-550 (2021).
[3] Iebed, D., Gökler, T., van Ingen, H., Conibear, A. C., ChemBioChem, 25, e20241023 (2024).
[4] Gajsek, O., Becker, C. F. W., Conibear, A. C., Chem. Eur. J. e202403676 (2024).
Bio
Anne Conibear is an Assistant Professor at TU Wien (Technical University of Vienna, Austria). She is originally from Zimbabwe and completed her B.Sc.(Hons) and M.Sc. in Chemistry (2010) at Rhodes University, South Africa. She then moved to the University of Queensland, Australia with an International Postgraduate Research Scholarship for her PhD (2014) with Prof. David Craik. During her PhD, she started working with peptides and focused on the synthesis, structure and activities of cyclic disulfide-rich peptides from mammals, the theta-defensins. In 2014, she was awarded an Interdisciplinary Cancer Research (Marie-Curie co-fund) postdoctoral fellowship at the University of Vienna, Austria, and worked with Prof. Christian Becker on targeted immune-stimulating molecules for cancer therapy. She returned to the University of Queensland in 2019 with a UQ Development Fellowship to start her independent research on the synthesis and structure of posttranslationally modified proteins. In 2022, she took up a tenure-track Assistant Professor position in Peptide and Protein Chemistry at TU Wien, Austria. Research in her group focuses on how posttranslational modifications regulate protein structure and biological function of intrinsically disordered proteins and regions.