1. Characterization of Unique Signature Sequences in the Divergent Maternal Protein Bcl2l10
- Author
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Germain Gillet, Abdel Aouacheria, François Penin, Aurélie Cornut-Thibaut, Yannis Guillemin, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ganivet, Agnès, Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
- Subjects
MESH : Cell Line ,MESH : Molecular Sequence Data ,Amino Acid Motifs ,MESH: Amino Acid Sequence ,MESH: Base Sequence ,MESH : Proto-Oncogene Proteins c-bcl-2 ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,MESH: INDEL Mutation ,protein sequence ,MESH: Amino Acid Motifs ,MESH: Protein Structure, Tertiary ,0302 clinical medicine ,INDEL Mutation ,Databases, Genetic ,genetic polymorphism ,MESH : Female ,MESH: Animals ,MESH: Genetic Variation ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,Peptide sequence ,MESH: Databases, Genetic ,MESH: Evolution, Molecular ,Sequence Deletion ,Genetics ,chemistry.chemical_classification ,0303 health sciences ,MESH : Amino Acid Sequence ,MESH : Sequence Alignment ,apoptosis ,Vertebrate ,MESH: Sequence Deletion ,Amino acid ,Proto-Oncogene Proteins c-bcl-2 ,MESH: Calcium ,030220 oncology & carcinogenesis ,Female ,MESH : Protein Structure, Tertiary ,MESH : Amino Acid Motifs ,Molecular Sequence Data ,MESH: Sequence Alignment ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Sequence alignment ,Biology ,Cell Line ,MESH: Oocytes ,Evolution, Molecular ,03 medical and health sciences ,Bcl-2 family ,MESH : Genetic Variation ,biology.animal ,evolution ,[SDV.BDD] Life Sciences [q-bio]/Development Biology ,Genetic variation ,Homologous chromosome ,Animals ,Humans ,MESH : HeLa Cells ,MESH : Evolution, Molecular ,Amino Acid Sequence ,MESH : Calcium ,MESH : Databases, Genetic ,Indel ,MESH : INDEL Mutation ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,MESH : Mutagenesis, Insertional ,calcium ,MESH: Humans ,MESH: Molecular Sequence Data ,Base Sequence ,MESH : Sequence Deletion ,MESH: Apoptosis ,MESH : Humans ,MESH : Oocytes ,Genetic Variation ,Protein Structure, Tertiary ,MESH: Cell Line ,Mutagenesis, Insertional ,MESH: Mutagenesis, Insertional ,MESH: Proto-Oncogene Proteins c-bcl-2 ,chemistry ,MESH: HeLa Cells ,Oocytes ,MESH : Base Sequence ,MESH : Animals ,Sequence Alignment ,MESH: Female ,MESH : Apoptosis ,HeLa Cells - Abstract
International audience; 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.
- Published
- 2011
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