The molecular grammar of protein disorder guiding genome-binding locations
Felix Jonas1, Miri Carmi1, Beniamin Krupkin1
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Abstract:
Intrinsically disordered regions (IDRs) direct transcription factors (TFs) towards selected genomic occurrences of their binding motif, as exemplified by budding yeast's Msn2. However, the sequence basis of IDR-directed TF binding selectivity remains unknown. To reveal this sequence grammar, we analyze the genomic localizations of >100 designed IDR mutants, each carrying up to 122 mutations within this 567-AA region. Our data points at multivalent interactions, carried by hydrophobic-mostly aliphatic-residues dispersed within a disordered environment and independent of linear sequence motifs, as the key determinants of Msn2 genomic localization. The implications of our results for the mechanistic basis of IDR-based TF binding preferences are discussed.
More Related Videos
Related Concept Videos
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....
From DNA to Protein
Ligand Binding and Linkage
Intrinsically Disordered Proteins
Conservation of Protein Domains Over Different Proteins
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...


