BioSAXS Characterisation of the Conformational Ensemble and Self-Association of the PCDH15 Cytoplasmic Region

We aim to characterise the conformational ensemble, self-association, and potential LLPS behaviour of the cytoplasmic region of Protocadherin-15 (PCDH15), essential for auditory mechanotransduction. Preliminary in-house and BM29 data confirm intrinsic disorder in CD2, while the extended CRCD2 construct shows monomer–dimer coexistence, altered dimensions, and concentration-dependent interactions. Using SEC-SAXS and batch BioSAXS across ionic strength, pH, and calcium conditions, we will resolve monomeric and dimeric scattering contributions and define how solution environment modulates compaction and association. A CD2-derived peptide will further benchmark MD simulations. This work will provide the first structural insight into the PCDH15 cytoplasmic region and support integrative modelling of IDPs.