GYF Domain

The GYF domain has so far not yet been unambiguously assigned to certain disease states. Nevertheless, overexpression of the GYF-containing protein CD2BP2 was observed in chronic fatigue syndrome (Kaushik et al. 2005), and the same protein was found to be overexpressed in estradiol-, 4-hydroxytamoxifen- and acolbifene-treated T47D breast cancer cells (Al Dhaheri et al. 2006). Independent of its possible role in these disease-related processes, GYF domain inhibition would be a valuable tool for deciphering its function within the spliceosome. Several proteins exist that are likely to be targeted by CD2BP2-GYF. A specific inhibitor in combination with pulldown experiments and proteomic analysis would enable the delineation of the relative contribution of PRM recognition to GYF domain function. Since the GYF domain contains a second, PRM-inde-pendent binding site for the U5 snRNP protein 15 K (Nielsen et al. 2007), site-specific blocking of the PRM pocket by peptides or small molecules is an effective strategy to achieve such de-convolution of a binary adaptor domain. Thereby, PRM recognition by the GYF domain could be a paradigmatic example of PRM recognition in the context of multiple binding events within a macromo-lecular complex.

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