The molecular grammar of protein disorder guiding genome-binding locations

Felix Jonas; Miri Carmi; Beniamin Krupkin; Joseph Steinberger; Sagie Brodsky; Tamar Jana; Naama Barkai

doi:10.1093/nar/gkad184

The molecular grammar of protein disorder guiding genome-binding locations

Nucleic Acids Res. 2023 Jun 9;51(10):4831-4844. doi: 10.1093/nar/gkad184.

Authors

Felix Jonas¹, Miri Carmi¹, Beniamin Krupkin¹, Joseph Steinberger¹, Sagie Brodsky¹, Tamar Jana¹, Naama Barkai¹

Affiliation

¹ Department 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Genomics
Intrinsically Disordered Proteins* / chemistry
Mutation
Protein Binding
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins* / metabolism
Transcription Factors* / metabolism

Substances

Intrinsically Disordered Proteins
Transcription Factors
MSN2 protein, S cerevisiae
Saccharomyces cerevisiae Proteins