Importantly, the results of our NMR and cell biology experiments suggest that phosphorylation at Thr231 (which is within the Tau PRD sequence that interacts with the BIN1 SH3 domain) weakens this interaction.
We found that unliganded TR binds tightly to DNA, and, we show for the first time that T3 weakens this interaction (4 fold) without affecting the cooperative nature of binding.
This suggests that Lys methylation may have little overall net effect or slightly weakens this interaction, as Ser contributes relatively little to the interaction relative to Leu [ 25].
Our results show that BIN1's SH3 domain interacts directly with the Tau PRD, and that Tau phosphorylation (notably at Thr231) weakens this interaction.
In this regard, we note that the site of one of the sae2∆ suppressors, P110, lies in the 'latching loop' region of eukaryotic Mre11 that is likely to mediate contacts with Xrs2 (Schiller et al, 2012), suggesting that, in this case, sae2Δ suppression might arise through weakening this interaction and dampening Tel1 activity.
Interaction of these two domains stabilizes the closed state of the Ca2+ release channel, and mutations in this region might weaken this interdomain interaction, leading to a decline of tight channel control, lowering of the barrier for Ca2+ release, and an increase in Ca2+ leakage from the SR (10).
Intriguingly, a MCPH mutation (E1235V) in the conserved C-terminal domain of CPAP (the so-called TCP-domain or G-Box) appeared to weaken this yeast-two-hybrid interaction (Tang et al., 2011).
This process could reduce the positive charge and weaken the interaction of histone with DNA, consequently, increasing the transcriptional activity.
Its binding is proposed to weaken the interaction of c-Jun to JNK by approximately 5-fold, without affecting the efficiency of phosphorylation within the complex.
