Characterization of unique signature sequences in the divergent maternal protein Bcl2l10

Insertions or deletions (indels) of amino acids residues have been recognized as an important source of genetic and structural divergence between paralogous Bcl-2 family members. However, these signature sequences have not so far been extensively investigated amongst orthologous Bcl-2 family proteins. Bcl2l10 is an antiapoptotic member of the Bcl-2 family that has evolved rapidly throughout the vertebrate lineage and which shows conserved abundant expression in eggs and oocytes. In this paper, we have unraveled two major sites of divergence between human Bcl2l10 and its vertebrate homologs. The first one provides length variation at the N-terminus (before the BH4 domain) and the second one is located between the predicted ?5-?6 pore-forming helices, providing an unprecedented case in the superfamily of helix-bundled pore-forming proteins. These two particular indels were studied phylogenetically and through biochemical and cell biological techniques, including truncation and site-directed mutagenesis. While deletion of the N-terminal extension had no significant functional impact in HeLa cells, our results suggest that the human Bcl2l10 protein evolved a calcium-binding motif in its ?5-?6 interhelical region by acquiring critical negatively charged residues. Considering the reliance of female eggs on calcium-dependent proteins and calcium-regulated processes and the exceptional longevity of oocytes in the primate lineage, we propose that this microstructural variation may be an adaptive feature associated with high maternal expression of this Bcl-2 family member.

Guillemin, Yannis
Cornut-Thibaut, AurÈlie
Gillet, Germain
Penin, FranÁois
Aouacheria, Abdel
Item Type: 
Journal Article
Publication Title: 
Molecular Biology and Evolution
Journal Abbreviation: 
Mol. Biol. Evol.
Publication Date: 
Publication Year: 
Library Catalog: 
NCBI Published Medical (?)
PMID: 21705382

Turabian/Chicago Citation

Yannis Guillemin, AurÈlie Cornut-Thibaut, Germain Gillet, FranÁois Penin and Abdel Aouacheria. 2011-12. "Characterization of unique signature sequences in the divergent maternal protein Bcl2l10." Molecular Biology and Evolution 28: 12: 3271-3283. 10.1093/molbev/msr152.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1093/molbev/msr152 | issn = 1537-1719 | volume = 28 | pages = 3271-3283 | last = Guillemin | first = Yannis | coauthors = Cornut-Thibaut, AurÈlie, Gillet, Germain, Penin, FranÁois, Aouacheria, Abdel | title = Characterization of unique signature sequences in the divergent maternal protein Bcl2l10 | journal = Molecular Biology and Evolution | date = 2011-12 | pmid = | pmc = }} </ref>