Discovering the bacterial antecedents of key transcription and apoptosis regulators in animals

Shalika Neelaveni
National Center for Biotechnology Information,
National Library of Medicine, National Institutes of Health

The death domain superfamily, comprising the death domain (DD) and others, is an important
component of the apoptotic pathways a component of programmed cell death (PCD). It was
found that the DD proteins might be combined with an uncharacterized domain which has been
claimed to be a nucleic acid binding domain (NABD) as per the Pfam database: Nucleic_acid_bd
(PF13820). Apart from general functional characterization, little is known about the specific
function performed by the NABD itself. The objectives of the investigation was to understand
the function of NABD, use “guilt by association” principle with the death-related domains to
understanding its biological role, and discover homologs along the way. To glean insights into
the role of the NABD, computational approaches were used to collect all the related members
through sequence searches (BLAST and PSI-BLAST). Further, all the globular domains that
were identified as co-occurring with the NABD were collected. The genomic and functional
contexts of these domains were then examined. Lineage specific expansions in many taxonomic
lineages and the Crassostrea expansion were examined in this study. This research resulted in
detection of a bacterial antecedents of one more components of the eukaryotic apoptosis
machinery. A new nucleic acid binding domain (NABD) that is part of death domain superfamily
of proteins responsible for apoptosis was characterized and then unified with the TRADD_N
domain (another adaptor domain of eukaryotic apoptotic machinery). This study led to detection
of bacterial antecedents of one more component of the apoptosis machinery, and redefined the
boundaries of NABD to decipher its functional role.