Poster Presentation The 43rd Lorne Conference on Protein Structure and Function 2018

Investigation of BCL-RAMBO, a poorly characterised BCL-2 family member (#227)

Kristen Scicluna 1 , Jonathan P Bernardini 1 , Ahmad Wardak 1 , Richard W Birkinshaw 1 , Angus D Cowan 1 , Jason M Brouwer 1 , Grant Dewson 1 , Peter E Czabotar 1
  1. WEHI, Parkville, VIC, Australia

Apoptosis is a process of programmed cell suicide regulated by proteins of the BCL-2 family. Interplay between pro- and anti-apoptotic BCL-2 family proteins determines cell fate. BCL-2 family members have been the focus of extensive investigation as their dysregulation is a major driver of diseases such as cancer, nonetheless, several members remain poorly characterised. BCL-RAMBO is one such member sharing sequence and predicted structural homology with that of other BCL-2 family proteins. This 485-amino acid protein possesses all four BCL-2 homology (BH) domains characteristic of the BCL-2 family, a C-terminal transmembrane (TM) domain responsible for mitochondrial localisation and an atypical 250-amino acid extension (BHNo domain) that is predicted to be disordered. The function of BCL-RAMBO remains ambiguous with conflicting reports suggesting both pro- and anti- apoptotic roles as well as a role in mitophagy, the selective elimination of mitochondria. Evidence of protein:protein interactions between BCL-RAMBO and other BCL-2 family is lacking, however, a putative interaction with the mitophagy mediator LC3 has been reported1. As BCL-RAMBO expression has been implicated in glioblastoma, acute lymphoblastic leukaemia and rectal adenocarcinoma, clarification regarding its structure and function are of great interest.

Here, we utilise complementary structural and functional approaches to provide clarification regarding the activity of BCL-RAMBO in apoptosis, and to elucidate potential binding partners within the BCL-2 family. These findings detail preliminary conditions with which to study BCL-RAMBO in order to interrogate its potential role in disease and to complete our portrait of the BCL-2 family of proteins.


  1. Murakawa, T., Yamaguchi, O., Hashimoto, A., Hikoso, S., Takeda, T., Oka, T. et al. Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy and mitochondrial fragmentation. Nature Communications 6, 1–14 (2015).