Figure 2. Charged residues influence IDR dimensions in live cells.
(A) Charged residues of the same polarity are repulsive, while charged residues of opposite polarity are attractive. (B) We focus on sequences in which charged residues are either evenly distributed across the sequence (left) or clustered together with like charges (right). (C) FRET efficiency Ef for IDRs with evenly distributed charged residues and a net charge of −0.3 or +0.3, increasing the fraction of charged residues (FCR) in the sequence leads to ensemble expansion, in line with prior in vitro work. (D) Ef for IDRs with clustered charged residues and a net charge of −0.3 or +0.3, increasing the percentage of charged residues leads to compaction for negatively charged sequences and expansion for positively charged sequences. For all four pairs, the FCR=0.3 sequences contain only one type of charged residue, while the FCR=0.6 sequences contain both. (E) For IDRs with a net neutral charge, increasing the fraction of charged residues when charged residues are evenly spaced or clustered leads to, at most, a small increase in IDR dimensions. (F) For IDRs with an FRC of 0.3, systematically titrating the net charge from −0.3 to 0 to +0.3 leads, in most cases, to a gradual compaction. The two sets where there is a small expansion (12 to 14) or non-significant compaction (11 to 13) involve the acidic sequence possessing several aromatic residues, likely making it more compact than it might otherwise be. (G) For IDRs with 60% charged residues, systematically titrating the net charge from −0.3 to 0 to +0.3 leads, in most cases, to a gradual compaction. N for each violin plot is in Table S5.