Functional assessment of protein variants in structured domains by fluorescence cross-correlation spectroscopy.

ABSTRACT: With the expanding catalogue of novel disease-genes, there is an increasing need to establish the significance of potential disease-causing variants. Based on the idea that pathogenic variants in structured protein domains disturb folding and association with macromolecular assemblies, we employed Fluorescence Correlation and Cross-Correlation Spectroscopy (FCS and FCCS) to assess in vivo protein complex formation. Since the molecular underpinning of BRCA-associated breast and ovarian cancers is well defined and data from a recent genome editing screening allowed us to compare variant binding data with a reliable functional HRD test in addition to ClinVar and AlphaMissense data, we examined the binding of mutated full-length BRCA1 or isolated RING and BRCT domains to BARD1 and RBBP8, respe

SUBMITTER: Mateu-Regue A 

PROVIDER: S-EPMC12867984 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature