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

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

Department of Molecular Genetics

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	4831-4844
Number of pages	14
Journal	Nucleic acids research
Volume	51
Issue number	10
DOIs	https://doi.org/10.1093/nar/gkad184
State	Published - 9 Jun 2023

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nb_NucleicAcidsRes_MolecularGrammarofProtein_PV_2023Final published version, 2.2 MBLicense: CC BY-NC

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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.",

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AU - Krupkin, Beniamin

AU - Steinberger, Joseph

AU - Brodsky, Sagie

AU - Jana, Tamar

AU - Barkai, Naama

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AB - 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.

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The molecular grammar of protein disorder guiding genome-binding locations

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