title: Characterization of unique signature sequences in the divergent maternal protein Bcl2l10.
abstract: 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 α5-α6 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 α5-α6 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.
authors.affiliation: Institut de Biologie et Chimie des Protéines, UMR 5086 CNRS, Université de Lyon, IFR 128/UMS3444 BioSciences Gerland-Lyon Sud, Lyon Cedex, France.
authors.forename: Yannis
authors.initials: Y
authors.lastname: Guillemin
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cornut-Thibaut
authors.forename: Germain
authors.initials: G
authors.lastname: Gillet
authors.forename: François
authors.initials: F
authors.lastname: Penin
authors.forename: Abdel
authors.initials: A
authors.lastname: Aouacheria
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D030541:Databases, Genetic; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D006367:HeLa Cells; D006801:Humans; D054643:INDEL Mutation; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics; D009865:Oocytes; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D016415:Sequence Alignment; D017384:Sequence Deletion
chemical_list: C117144:BCL2-like 10 protein; D019253:Proto-Oncogene Proteins c-bcl-2; D002118:Calcium