Proteome-scale characterisation of motif-based interactome rewiring by disease mutations

ABSTRACT: Whole genome and exome sequencing are reporting on hundreds of thousands of missense mutations. Taking a pan-disease approach, we explored how mutations in the intrinsically disordered regions (IDRs) break or generate protein interactions mediated by short linear motifs. We created a peptide-phage display library tiling ~57,000 peptides from the IDRs of the human proteome overlapping 12,301 single nucleotide variant associated with diverse phenotypes including cancer, metabolic diseases and neurological diseases. By screening 80 human proteins, we identified 366 mutation-modulated interactions, with half of the mutations diminishing binding, and half enhancing binding or creating novel interaction interfaces. The effects of the mutations were confirmed by affinity measurements. In cellular

SUBMITTER: Ms Johanna Kliche 

PROVIDER: S-SCDT-10_1038-S44320-024-00055-4 | biostudies-other |

REPOSITORIES: biostudies-other