Multimodular proteins and their interactions in cancer and molecular signalling processes
Title: Multimodular proteins and their interactions in cancer and molecular signalling processes
SNIC Project: LiU-2018-13
Project Type: LiU Compute
Principal Investigator: Maria Sunnerhagen <>
Affiliation: Linköpings universitet
Duration: 2018-06-25 – 2020-07-01
Classification: 10601


In this project, we study the conformational dynamics and interactions of protein domains involved in tumor formation, both directly and in the indirect regulation of processes involved in this disease. While structure determinations using crystallography and NMR can provide three-dimensional coordinates of protein atoms, much of their function is in fact attributed to the dynamics inherent to these molecular assemblies. Such dynamics has increasingly been found to contribute in major ways to allosteric functions in proteins, i e how binding to one part of a protein domain can affect the biological function (catalysis, binding etc) in a distant site. To analyse this, advanced computational methodologies are required. Furthermore, our structural calculations where experimental diffraction data (x-ray) or chemical shifts/NOEs (NMR) are transformed into three-dimensional coordinates require immediate access to structural calculation software. For this reason we have developed the compute software platform PReSTO described below, which is a unique collaboration between NSC and MAXIV within biocompute. Key references for our recent work include: Structure (2018) Multivalent Interactions with Fbw7 and Pin1 Facilitate Recognition of c-Jun by the SCFFbw7 Ubiquitin Ligase. Csizmok V, Montecchio M, Lin H, Tyers M, Sunnerhagen M, Forman-Kay JD. JBC (2018, in review): Allosterically engaged capture of a ubiquitination-targeted lysine by the UBE2E1-TRIM21 E2-E3 complex. Anandapadamanaban, Kyriadikis, Csizmok, Wallenhammar, Espinosa, Round, Trewhella, Moche, Wahren-Herlenius & Sunnerhagen. PLoS One (2017): Solution NMR structure of the TRIM21 B-box2 and identification of residues involved in its interaction with the RING domain. Wallenhammar, Anandapadamanaban, Lemak, Mirabello, Lundström, Wallner & Sunnerhagen. Structure (2016): Mutation-induced population shift in the MexR conformational ensemble disengages DNA binding: A novel mechanism for MarR family derepression. Anandapadamanabn, Pilstål, Andresen, Trewhella, Moche, Wallner & Sunnerhagen. Structure (2015): Pre-anchoring of Pin1 to unphosphorylated c-Myc in a fuzzy complex regulates c-Myc activity. Helander, Montecchio, Pilstål, Su, Kuruvilla, Elven, Ziauddin, Anandapadamanaban, Cristobal, Lundström, Sears, Wallner & Sunnerhagen. Nature Structural and Molecular Biology (2013): High-resolution structure of TBP with TAF1 reveals anchoring patterns in transcription. Anandapadamanaban, Andresen, Helander, Ohyama, Siponen, Lundström, Kokubo, Ikura, Moche & Sunnerhagen.