Structure and Recognition in the BARS/CtBP-dependent Transcription Regulation

BARS/CtBP3 is a dual function protein acting as acyl-transferase in the Golgi apparatus (supporting membrane reshaping and vesicle traffic), and as transcription co-repressor, in the nucleus, through the interaction with several enzymatic partners (e.g. histone deacetylases, HDACs). BARS/CtBP3 is based on a 3-domain structure, hosting a classical dehydrogenase fold. Regulation of the two activities is achieved through competitive binding of NAD(H)/acyl-CoA, association equilibria, SUMO-ylation, and eventually through recognition of specific sequence motifs in the interacting partners. Binding of specific transcription factors to each subunit in the dimeric BARS/CtBP3, through a PXDLS sequence motif, is considered one of the basic mechanisms to recruit HDACs, and modify the chromatin structure, with ensuing transcription repression. Structural considerations and mutant analyses indicate that different recognition sites are present on BARS/CtBP3 surface, in keeping with its pivotal role within a nuclear protein complex hosting more than twenty different proteins.