Structural characterization of BICC1 and fragment-based screening by WAC-MS

Bicaudal C homolog 1 (BICC1) is an RNA-binding protein involved in direct mediation of post-transcriptional gene regulation as part of a major regulatory complex, and that has been related to polycystic kidney disease1,2 and depression. We intend to improve knowledge around BICC1 role, by linking biological data already obtained from IP and CLIP-Seq to structural data generated by crystallography and binding experiments, potentially allowing development of chemical inhibitors or a probe. Soluble versions of BICC1 obtained from bacteria were used in biochemical binding assays and crystallization trials. BICC1 retains the capacity of interacting with both DNA and RNA oligos, and the structure of KH1 domain was confirmed. Fragment screening by Weak Affinity Chromatography coupled to Mass Spectrometry (WAC-MS) revealed ligands with KD values below millimolar range, that are being confirmed by orthologous methods, and sent to crystallographic trials to investigate the binding mode and support the development of new derivatives.