蛋白质无序的分子语法指导基因组结合位置。

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.

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

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.

无规则区域 (IDR) 将转录因子 (TF) 引导至其结合基序的特定基因组位置，芽殖酵母的 Msn2 就是一个例子。然而，IDR 导向的 TF 结合选择性的序列基础仍然未知。为了揭示这种序列语法，我们分析了 >100 个设计的 IDR 突变体的基因组定位，每个突变体在这个 567-AA 区域内携带多达 122 个突变。我们的数据表明，多价相互作用由分散在无规环境中的疏水性脂肪族残基携带，与线性序列基序无关，是 Msn2 基因组定位的关键决定因素。我们的结果对基于 IDR 的 TF 结合偏好的机制基础具有重要意义。