Bioinformatics Seminars

Bioinformatics Seminar

Time: 10:45am Tuesdays.
Level 7 Seminar Room 2, WEHI1

2 October 2018

Quantitative maps of protein sequence space to investigate early evolution superfamilies

Thomas Shafee
La 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).

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