The Bcl-2 Family: Ancient Origins, Conserved Structures, and Divergent Mechanisms

Intrinsic apoptosis, the response to intracellular cell death stimuli, is regulated by the interplay of the B-cell lymphoma 2 (Bcl-2) family and their membrane interactions. Bcl-2 proteins mediate a number of processes including development, homeostasis, autophagy, and innate and adaptive immune responses and their dysregulation underpins a host of diseases including cancer. The Bcl-2 family is characterized by the presence of conserved sequence motifs called Bcl-2 homology motifs, as well as a transmembrane region, which form the interaction sites and intracellular location mechanism, respectively. Bcl-2 proteins have been recognized in the earliest metazoans including Porifera (sponges), Placozoans, and Cnidarians (e.g., Hydra). A number of viruses have gained Bcl-2 homologs and subvert innate immunity and cellular apoptosis for their replication, but they frequently have very different sequences to their host Bcl-2 analogs. Though most mechanisms of apoptosis initiation converge on activation of caspases that destroy the cell from within, the numerous gene insertions, deletions, and duplications during evolution have led to a divergence in mechanisms of intrinsic apoptosis. Currently, the action of the Bcl-2 family is best understood in vertebrates and nematodes but new insights are emerging from evolutionarily earlier organisms. This review focuses on the mechanisms underpinning the activity of Bcl-2 proteins including their structures and interactions, and how they have changed over the course of evolution.

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Conserved sequence motifs among bacterial, eukaryotic, and archaeal phosphatases that define a new phosphohydrolase superfamily

Protein Science ◽

10.1002/pro.5560070722 ◽

1998 ◽

Vol 7 (7) ◽

pp. 1647-1652 ◽

Cited By ~ 96

Author(s):

Maria Cristina Thaller ◽

Serena Schippa ◽

Gian Maria Rossolini

Keyword(s):

Sequence Motifs ◽

Conserved Sequence ◽

Conserved Sequence Motifs

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Identification and Analysis of Novel Amino-Acid Sequence Repeats inBacillus anthracisstr.AmesProteome Using Computational Tools

Comparative and Functional Genomics ◽

10.1155/2007/47161 ◽

2007 ◽

Vol 2007 ◽

pp. 1-23 ◽

Cited By ~ 2

Author(s):

G. R. Hemalatha ◽

D. Satyanarayana Rao ◽

L. Guruprasad

Keyword(s):

Amino Acid ◽

Amino Acid Residue ◽

Protein Sequence ◽

Amino Acid Residues ◽

Sequence Motifs ◽

Computational Tools ◽

Conserved Sequence ◽

Conserved Sequence Motifs ◽

Multiple Copies ◽

Domain 3

We have identified four repeats and ten domains that are novel in proteins encoded by theBacillus anthracisstr.Amesproteome using automated in silico methods. A “repeat” corresponds to a region comprising less than 55-amino-acid residues that occur more than once in the protein sequence and sometimes present in tandem. A “domain” corresponds to a conserved region with greater than 55-amino-acid residues and may be present as single or multiple copies in the protein sequence. These correspond to (1) 57-amino-acid-residue PxV domain, (2) 122-amino-acid-residue FxF domain, (3) 111-amino-acid-residue YEFF domain, (4) 109-amino-acid-residue IMxxH domain, (5) 103-amino-acid-residue VxxT domain, (6) 84-amino-acid-residue ExW domain, (7) 104-amino-acid-residue NTGFIG domain, (8) 36-amino-acid-residue NxGK repeat, (9) 95-amino-acid-residue VYV domain, (10) 75-amino-acid-residue KEWE domain, (11) 59-amino-acid-residue AFL domain, (12) 53-amino-acid-residue RIDVK repeat, (13) (a) 41-amino-acid-residue AGQF repeat and (b) 42-amino-acid-residue GSAL repeat. A repeat or domain type is characterized by specific conserved sequence motifs. We discuss the presence of these repeats and domains in proteins from other genomes and their probable secondary structure.

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Conserved sequence motifs, alignment, and secondary structure for the third domain of animal 12S rRNA

Molecular Biology and Evolution ◽

10.1093/oxfordjournals.molbev.a025552 ◽

1996 ◽

Vol 13 (1) ◽

pp. 150-169 ◽

Cited By ~ 181

Author(s):

R. E. Hickson ◽

C. Simon ◽

A. Cooper ◽

G. S. Spicer ◽

J. Sullivan ◽

...

Keyword(s):

Secondary Structure ◽

12S Rrna ◽

Sequence Motifs ◽

Conserved Sequence ◽

The Third ◽

Conserved Sequence Motifs

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SAND, a New Protein Family: From Nucleic Acid to Protein Structure and Function Prediction

Comparative and Functional Genomics ◽

10.1002/cfg.93 ◽

2001 ◽

Vol 2 (4) ◽

pp. 226-235 ◽

Cited By ~ 5

Author(s):

Amanda Cottage ◽

Yvonne J. K. Edwards ◽

Greg Elgar

Keyword(s):

Genomic Sequence ◽

Protein Family ◽

Sequence Motifs ◽

Est Database ◽

Computational Tools ◽

Conserved Sequence ◽

Conserved Sequence Motifs ◽

And Function ◽

New Protein ◽

Genomic Organisation

As a result of genome, EST and cDNA sequencing projects, there are huge numbers of predicted and/or partially characterised protein sequences compared with a relatively small number of proteins with experimentally determined function and structure. Thus, there is a considerable attention focused on the accurate prediction of gene function and structure from sequence by using bioinformatics. In the course of our analysis of genomic sequence fromFugu rubripes, we identified a novel gene,SAND, with significant sequence identity to hypothetical proteins predicted inSaccharomyces cerevisiae, Schizosaccharomyces pombe, Caenorhabditis elegans, aDrosophila melanogastergene, and mouse and human cDNAs. Here we identify a furtherSANDhomologue in human andArabidopsis thalianaby use of standard computational tools. We describe the genomic organisation ofSANDin these evolutionarily divergent species and identify sequence homologues from EST database searches confirming the expression of SAND in over 20 different eukaryotes. We confirm the expression of two different SAND paralogues in mammals and determine expression of one SAND in other vertebrates and eukaryotes. Furthermore, we predict structural properties of SAND, and characterise conserved sequence motifs in this protein family.

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