Bioinformatics Seminar
Time:
Venue: Na
2 October 2018
NaQuantitative maps of protein sequence space to investigate early evolution superfamilies
Thomas ShafeeLa Trobe University
Defensins are extremely sequence-diverse ; small ; disulphide-rich proteins found across the eukaryotes ; best known for their host-defence functions. Additionally ; defensin-related families have been recruited to roles as signalling molecules ; toxins ; metal binders ; and enzyme inhibitors. The evolutionary origins of the defensins have remained largely unknown due to their extreme sequence divergence ; short length ; and frequent insertions and deletions.
To address this ; we have developed techniques to make quantitative maps of local regions of protein sequence space with sequences arranged based on their biophysical properties. Combined with structure similarity networks ; these maps have uncovered several unusual features of the defensins.
The defensins consist of two independent superfamilies with extensive convergent evolution. Despite their near-random sequences ; there are clear clusters with shared properties which also strongly correlate to known functions. Analyses also indicate that a recently solved minimal 2-disulphide version of the fold likely reflects an ancestral form of the cis-defensin superfamily. Together these investigations shed light on this unusual and widespread superfamily ; and may indicate a more general route for the early origins of cystine-rich proteins after their de novo gene birth.
These techniques are now being adapted for globular proteins (e.g. proteases ; fasciclins ; and glycosyl transferases) ; and intrinsically disordered peptides (e.g. fungal effectors and Arabinogalactan proteins).