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Our data thus indicate that both basic clusters of IFNγ are fundamental for the interaction with LcrV, with a strong involvement of the most distal one (D2).
The binary basic clusters are first selected for constructing cluster lines.
The analysis confirmed the basic cluster assignments seen with whole genome nucleotide analysis and revealed distant relationships between the E, F, G and I clusters discussed in more detail below.
The analysis confirmed the basic cluster assignments seen with whole genome nucleotide analysis and revealed distant relationships between the TP21-like D, gamma d'Herelle-like E, and IEBH-like F cluster phages discussed in more detail below.
An even more pronounced phenomenon was observed when IFNγ basic cluster D2 was modified, with a single mutation at position 140 almost completely abolishing LcrV recognition.
With the basic clustering method, the cost can be reduced only by up to 35%%.
Interestingly, in the same crystal structure, it was observed that certain SV40 T-antigen residues upstream of the basic cluster also make specific contacts with importin α that are distinct from the binding sites of classical NLSs [ 61].
More importantly, it is observed that the inclusion of coverage and capacity criteria has a larger impact on the basic clustering method than on the method with reclustering.
We further confirmed the importance of the basic cluster flanking R306 by performing EMSAs with two other RTT-causing point mutations: arginine to histidine at residue 306 (R306H) and lysine to glutamic acid at residue 304 (K304E), both of which remove a basic charge from the cluster (Christodoulou et al., 2003).
Full-length MeCP2 (gray) with the MBD (blue), TRD (red), and basic cluster (yellow) is depicted.
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