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Modelling GRNs under different experimental conditions, different tissues or ecotypes, where different but overlapping sets of transcription factors are expected to bind in the different treatments, with a limited number of TFs binding under any given condition/tissue/ecotype.
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The reasons for this differential APC response are surely bound up in the different in vivo APC function of DC and B cells.
This multicompartmentalization of DISC1 within the cell implies that it performs different roles and may bind different proteins in the different cellular components and thus have roles in a number of cellular processes.
To verify this intuitive explanation, we investigated the amounts of free CLV3 and bound CRN receptors in the different clv1 mutants.
This is interesting, given that the N-terminal Nlys residue in ADP3 was not critical for IgY binding, possibly suggesting that the screening hits bind in a different fashion to the antibodies than does ADP3.
In addition, different substrates bind in different regions of the large promiscuous binding site, so it is challenging to understand how drugs bound at different sites can communicate with the NBDs to stimulate ATP hydrolysis.
Two of the motifs (RxxPxxP and PxxxPR) were found to bind in two different orientations with the peptides flipped ~180° in the binding sites.
Alternatively, l-serine may allosterically bind in a different location, causing the C-terminal Cys 458 to be released from the Fe S cluster and subsequently to bind to His 124 and Asn 126, which could serve as a latch to prevent it from interfering with subsequent substrate binding at the active site.
Further, when a regulatory motif is not palindromic (motifs in this study are not palindromic), the cognate protein is likely to bind in a different orientation (relative to the TSS) to, for example, a CACA motif on the coding strand, as compared to a CACA motif on the non-coding strand.
Fig. 4 Proteins that are problematic for interaction fingerprint scoring: a PARP (1efy@pdb) has small ligands making only few interactions; b AChE [1acj@pdb, with overlay of ligands from 1acj (orange), 2j3q (yellow), 5bwc (violet), 1gpk (green) and 1gqr (red)] has structurally dissimilar ligands that bind in different parts of the binding site.
ChIP experiments have shown that NF-Y and p300 are dynamically bound to target promoters in the different phases of the cell cycle [16], [44].
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