Bioinformatics

 

We take a structural bioinformatics approach to study Ub recognition.

We recently developed an algorithm to identify hidden UBDs with the PDB (to learn more see our EMBO J paper 2013). 

Using this tool we identified human ALIX-V as a bona-fide UBD. 

ALIX links between Apoptosis-Linked Gene-2 (ALG-2), the Endosomal Sorting Complexes Required for Transport (ESCRT) complexes, and neuronal death.

Morever, ALIX plays a pivotal role in ubiquitylated-cargo trafficking at the MVB, in cytokinesis  and retrovirus (like HIV) budding.

 

We demonstrated that ALIX-V mutations that abrogate Ub binding, significantly affect retrovirus budding.

 

We collaborate with Haim Wolfson to identify additional UBDs.

 

We currently use the algorithm to study additional UBDs. For example below see how the algorithm identified the Rpn10-vWA domain as UBD at the same site we found in the crystal structure.

 

We also use other bioinformatic tools, usually as an initial study, to predict our downstream targets.