Protein regulation at atomic resolution: Insights into protein posttranslational modifications using NMR spectroscopy

Presented by Dr Anne Conibear, UQ Development Fellow, School of Biomedical Sciences

Protein complexity is exponentially increased by posttranslational modifications (PTMs). A delicate balance between attachment and removal of PTMs controls fundamental cellular processes such as transcription and cell signaling and can lead to disease if it malfunctions, making it crucial to understand at a molecular level how PTMs control protein functions. My research aims to combine chemical protein synthesis with structural biology to understand how PTMs lead to structural changes that result in functional changes in proteins. Chemical protein synthesis can provide unique access to site-specifically modified and segmentally labelled proteins, and NMR spectroscopy can provide structural, dynamic and mechanistic information on proteins at atomic resolution. I will discuss the distinctive signatures of PTMs in NMR spectra and use HMGN1 as a model intrinsically disordered protein – a high mobility group nucleosome-binding protein involved in remodeling chromatin and regulating transcription. Using site-specifically modified and segmentally labelled HMGN1 variants, we can study the effects of PTMs on the structural and dynamic properties of HMGN1 using NMR spectroscopy. Integrating chemical protein synthesis with structural biology allows us to gain new insights into the effects of PTMs on protein structure, dynamics and regulation of biological activity.

Anne Conibear 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 for her PhD (2011 – 2014) with Prof. David Craik, focusing on the structural characterisation and applications of cyclic disulfide-rich peptides from mammals, the theta-defensins. In 2014, she was awarded an Interdisciplinary Cancer Research (INDICAR) postdoctoral fellowship at the University of Vienna and worked on targeted immune-stimulating molecules for cancer therapy, collaborating with Syntab Therapeutics GmbH. She has recently returned to UQ with a UQ Development Fellowship at the School of Biomedical Sciences to start an independent project on the synthesis and structure of posttranslationally modified proteins.