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Molecular evolution and functional divergence of the Ca(2+) sensor protein in store-operated Ca(2+) entry: stromal interaction molecule.

Cai X - PLoS ONE (2007)

Bottom Line: Human STIMs and invertebrate STIM share several functionally important protein domains, but diverge significantly in the C-terminus.STIMs were subsequently subjected to one round of gene duplication as early as in the Euteleostomi lineage in vertebrates, with a second round of fish-specific gene duplication.After duplication, STIM-1 and STIM-2 molecules appeared to have undergone purifying selection indicating strong evolutionary constraints within each group.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, United States of America. xinjiang.cai@duke.edu

ABSTRACT
Receptor-mediated Ca(2+) signaling in many non-excitable cells initially induces Ca(2+) release from intracellular Ca(2+) stores, followed by Ca(2+) influx across the plasma membrane. Recent findings have suggested that stromal interaction molecules (STIMs) function as the Ca(2+) sensor to detect changes of Ca(2+) content in the intracellular Ca(2+) stores. Human STIMs and invertebrate STIM share several functionally important protein domains, but diverge significantly in the C-terminus. To better understand the evolutionary significance of STIM activity, phylogenetic analysis of the STIM protein family was conducted after extensive database searching. Results from phylogeny and sequence analysis revealed early adaptation of the C-terminal divergent domains in Urochordata, before the expansion of STIMs in Vertebrata. STIMs were subsequently subjected to one round of gene duplication as early as in the Euteleostomi lineage in vertebrates, with a second round of fish-specific gene duplication. After duplication, STIM-1 and STIM-2 molecules appeared to have undergone purifying selection indicating strong evolutionary constraints within each group. Furthermore, sequence analysis of the EF-hand Ca(2+) binding domain and the SAM domain, together with functional divergence studies, identified critical regions/residues likely underlying functional changes, and provided evidence for the hypothesis that STIM-1 and STIM-2 might have developed distinct functional properties after duplication.

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Structural analysis of the EF-hand domain and the SAM domain of STIMs.A. Sequence alignment of the EF-hand domain of representative STIM proteins and the chicken troponin C site III sequence (PDB entry 1CTA). The structural characteristics of 1CTA including two α-helices and the central Ca2+-binding loop are indicated above the sequence alignment. The positions of Ca2+ binding ligands are indicated with dark circle symbols below the alignment. The three residues of the β-sheet structure are marked with asterisk symbols. B. Sequence alignment of the SAM domain of representative STIM proteins and PDB entry 1V85. The two hydrophobic residues (Leu216 and Leu218 in IV85) at the oligomeric interface of SAM domains are indicated with asterisk symbols. One acidic residue (Glu185 in IV85) possibly affecting the aggregation state of SAM domains [39] is also indicated.
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pone-0000609-g004: Structural analysis of the EF-hand domain and the SAM domain of STIMs.A. Sequence alignment of the EF-hand domain of representative STIM proteins and the chicken troponin C site III sequence (PDB entry 1CTA). The structural characteristics of 1CTA including two α-helices and the central Ca2+-binding loop are indicated above the sequence alignment. The positions of Ca2+ binding ligands are indicated with dark circle symbols below the alignment. The three residues of the β-sheet structure are marked with asterisk symbols. B. Sequence alignment of the SAM domain of representative STIM proteins and PDB entry 1V85. The two hydrophobic residues (Leu216 and Leu218 in IV85) at the oligomeric interface of SAM domains are indicated with asterisk symbols. One acidic residue (Glu185 in IV85) possibly affecting the aggregation state of SAM domains [39] is also indicated.

Mentions: In fish genomes, STIM underwent a second round of duplications that resulted in, as far as can be ascertained in the current database, four copies of STIM molecules in each fish genome (Fig. 1 and Table S1). The fish-specific genome duplication is speculated to have occurred approximately 350 million years ago, after splitting from other vertebrates [25]. While possibly due to functional redundancy, most fish-specific duplicated genes were subsequently lost, the remaining duplicated genes might have evolved new functions. Indeed, sequence analysis of these duplicated fish STIMs reveals substantial sequence divergence even in the conserved protein domains (Figs. 3 and 4). The Orai protein family also exhibits fish-specific duplications in the Orai-1 group [3]. It remains intriguing if duplicated Orai and STIM molecules specific in the fish genomes cooperate to perform as yet uncharacterized, novel functions.


Molecular evolution and functional divergence of the Ca(2+) sensor protein in store-operated Ca(2+) entry: stromal interaction molecule.

Cai X - PLoS ONE (2007)

Structural analysis of the EF-hand domain and the SAM domain of STIMs.A. Sequence alignment of the EF-hand domain of representative STIM proteins and the chicken troponin C site III sequence (PDB entry 1CTA). The structural characteristics of 1CTA including two α-helices and the central Ca2+-binding loop are indicated above the sequence alignment. The positions of Ca2+ binding ligands are indicated with dark circle symbols below the alignment. The three residues of the β-sheet structure are marked with asterisk symbols. B. Sequence alignment of the SAM domain of representative STIM proteins and PDB entry 1V85. The two hydrophobic residues (Leu216 and Leu218 in IV85) at the oligomeric interface of SAM domains are indicated with asterisk symbols. One acidic residue (Glu185 in IV85) possibly affecting the aggregation state of SAM domains [39] is also indicated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1904252&req=5

pone-0000609-g004: Structural analysis of the EF-hand domain and the SAM domain of STIMs.A. Sequence alignment of the EF-hand domain of representative STIM proteins and the chicken troponin C site III sequence (PDB entry 1CTA). The structural characteristics of 1CTA including two α-helices and the central Ca2+-binding loop are indicated above the sequence alignment. The positions of Ca2+ binding ligands are indicated with dark circle symbols below the alignment. The three residues of the β-sheet structure are marked with asterisk symbols. B. Sequence alignment of the SAM domain of representative STIM proteins and PDB entry 1V85. The two hydrophobic residues (Leu216 and Leu218 in IV85) at the oligomeric interface of SAM domains are indicated with asterisk symbols. One acidic residue (Glu185 in IV85) possibly affecting the aggregation state of SAM domains [39] is also indicated.
Mentions: In fish genomes, STIM underwent a second round of duplications that resulted in, as far as can be ascertained in the current database, four copies of STIM molecules in each fish genome (Fig. 1 and Table S1). The fish-specific genome duplication is speculated to have occurred approximately 350 million years ago, after splitting from other vertebrates [25]. While possibly due to functional redundancy, most fish-specific duplicated genes were subsequently lost, the remaining duplicated genes might have evolved new functions. Indeed, sequence analysis of these duplicated fish STIMs reveals substantial sequence divergence even in the conserved protein domains (Figs. 3 and 4). The Orai protein family also exhibits fish-specific duplications in the Orai-1 group [3]. It remains intriguing if duplicated Orai and STIM molecules specific in the fish genomes cooperate to perform as yet uncharacterized, novel functions.

Bottom Line: Human STIMs and invertebrate STIM share several functionally important protein domains, but diverge significantly in the C-terminus.STIMs were subsequently subjected to one round of gene duplication as early as in the Euteleostomi lineage in vertebrates, with a second round of fish-specific gene duplication.After duplication, STIM-1 and STIM-2 molecules appeared to have undergone purifying selection indicating strong evolutionary constraints within each group.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, United States of America. xinjiang.cai@duke.edu

ABSTRACT
Receptor-mediated Ca(2+) signaling in many non-excitable cells initially induces Ca(2+) release from intracellular Ca(2+) stores, followed by Ca(2+) influx across the plasma membrane. Recent findings have suggested that stromal interaction molecules (STIMs) function as the Ca(2+) sensor to detect changes of Ca(2+) content in the intracellular Ca(2+) stores. Human STIMs and invertebrate STIM share several functionally important protein domains, but diverge significantly in the C-terminus. To better understand the evolutionary significance of STIM activity, phylogenetic analysis of the STIM protein family was conducted after extensive database searching. Results from phylogeny and sequence analysis revealed early adaptation of the C-terminal divergent domains in Urochordata, before the expansion of STIMs in Vertebrata. STIMs were subsequently subjected to one round of gene duplication as early as in the Euteleostomi lineage in vertebrates, with a second round of fish-specific gene duplication. After duplication, STIM-1 and STIM-2 molecules appeared to have undergone purifying selection indicating strong evolutionary constraints within each group. Furthermore, sequence analysis of the EF-hand Ca(2+) binding domain and the SAM domain, together with functional divergence studies, identified critical regions/residues likely underlying functional changes, and provided evidence for the hypothesis that STIM-1 and STIM-2 might have developed distinct functional properties after duplication.

Show MeSH