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Comparison of the receptor FGFRL1 from sea urchins and humans illustrates evolution of a zinc binding motif in the intracellular domain.

Zhuang L, Karotki AV, Bruecker P, Trueb B - BMC Biochem. (2009)

Bottom Line: FGFRL1, the gene for the fifth member of the fibroblast growth factor receptor (FGFR) family, is found in all vertebrates from fish to man and in the cephalochordate amphioxus.Since it does not occur in more distantly related invertebrates such as insects and nematodes, we have speculated that FGFRL1 might have evolved just before branching of the vertebrate lineage from the other invertebrates (Beyeler and Trueb, 2006).A comparison of the intracellular domain between sea urchin and human FGFRL1 provides interesting insights into the shaping of a novel zinc binding domain.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Research, University of Bern, 3010 Bern, Switzerland. lei.zhuang@dkf.unibe.ch

ABSTRACT

Background: FGFRL1, the gene for the fifth member of the fibroblast growth factor receptor (FGFR) family, is found in all vertebrates from fish to man and in the cephalochordate amphioxus. Since it does not occur in more distantly related invertebrates such as insects and nematodes, we have speculated that FGFRL1 might have evolved just before branching of the vertebrate lineage from the other invertebrates (Beyeler and Trueb, 2006).

Results: We identified the gene for FGFRL1 also in the sea urchin Strongylocentrotus purpuratus and cloned its mRNA. The deduced amino acid sequence shares 62% sequence similarity with the human protein and shows conservation of all disulfides and N-linked carbohydrate attachment sites. Similar to the human protein, the S. purpuratus protein contains a histidine-rich motif at the C-terminus, but this motif is much shorter than the human counterpart. To analyze the function of the novel motif, recombinant fusion proteins were prepared in a bacterial expression system. The human fusion protein bound to nickel and zinc affinity columns, whereas the sea urchin protein barely interacted with such columns. Direct determination of metal ions by atomic absorption revealed 2.6 mole zinc/mole protein for human FGFRL1 and 1.7 mole zinc/mole protein for sea urchin FGFRL1.

Conclusion: The FGFRL1 gene has evolved much earlier than previously assumed. A comparison of the intracellular domain between sea urchin and human FGFRL1 provides interesting insights into the shaping of a novel zinc binding domain.

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Alignment of the FGFRL1 sequences from eight different species. Identical residues are boxed. The putative signal peptidase cleavage site is shown by an arrow. The three Ig-like domains are marked by brackets. The transmembrane domain is given by a stippled box. Conserved glycosylation sites (NXT) are indicated by asterisks. The relative positions of introns in the corresponding genes are shown by triangles. The sequence that was used for the preparation of the zinc-binding GST fusion protein is underlined. The accession numbers are: FishA (Takifugu rubripes A) BN000669, FishB (Takifugu rubripes B) BN000670, Chicken AJ535114, Frog (Silurana tropicalis) AJ616852, Human AJ277437, Mouse AJ293947, Lancelet (Branchiostoma floridae) AJ888866, Sea Urchin (Strongylocentrotus purpuratus) FN252817, Sea Squirt (Ciona intestinalis) XP_002125836. From the sea squirt sequence only the conserved domain (residues 112-456) is included.
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Figure 1: Alignment of the FGFRL1 sequences from eight different species. Identical residues are boxed. The putative signal peptidase cleavage site is shown by an arrow. The three Ig-like domains are marked by brackets. The transmembrane domain is given by a stippled box. Conserved glycosylation sites (NXT) are indicated by asterisks. The relative positions of introns in the corresponding genes are shown by triangles. The sequence that was used for the preparation of the zinc-binding GST fusion protein is underlined. The accession numbers are: FishA (Takifugu rubripes A) BN000669, FishB (Takifugu rubripes B) BN000670, Chicken AJ535114, Frog (Silurana tropicalis) AJ616852, Human AJ277437, Mouse AJ293947, Lancelet (Branchiostoma floridae) AJ888866, Sea Urchin (Strongylocentrotus purpuratus) FN252817, Sea Squirt (Ciona intestinalis) XP_002125836. From the sea squirt sequence only the conserved domain (residues 112-456) is included.

Mentions: The three Ig-like domains were aligned with the FGFRL1 sequences from five vertebrates and lancelet (Fig. 1). In the resulting multiple sequence alignment, all the cysteine residues that participate in disulfide-bond formation of the three Ig-like loops are conserved. In contrast, the attachment sites for asparagine-linked carbohydrates are not conserved. The C. intestinalis sequence contains a total of 7 glycosylation signals (NXT/S) from which only two match glycosylation sites in the vertebrate sequences.


Comparison of the receptor FGFRL1 from sea urchins and humans illustrates evolution of a zinc binding motif in the intracellular domain.

Zhuang L, Karotki AV, Bruecker P, Trueb B - BMC Biochem. (2009)

Alignment of the FGFRL1 sequences from eight different species. Identical residues are boxed. The putative signal peptidase cleavage site is shown by an arrow. The three Ig-like domains are marked by brackets. The transmembrane domain is given by a stippled box. Conserved glycosylation sites (NXT) are indicated by asterisks. The relative positions of introns in the corresponding genes are shown by triangles. The sequence that was used for the preparation of the zinc-binding GST fusion protein is underlined. The accession numbers are: FishA (Takifugu rubripes A) BN000669, FishB (Takifugu rubripes B) BN000670, Chicken AJ535114, Frog (Silurana tropicalis) AJ616852, Human AJ277437, Mouse AJ293947, Lancelet (Branchiostoma floridae) AJ888866, Sea Urchin (Strongylocentrotus purpuratus) FN252817, Sea Squirt (Ciona intestinalis) XP_002125836. From the sea squirt sequence only the conserved domain (residues 112-456) is included.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2806250&req=5

Figure 1: Alignment of the FGFRL1 sequences from eight different species. Identical residues are boxed. The putative signal peptidase cleavage site is shown by an arrow. The three Ig-like domains are marked by brackets. The transmembrane domain is given by a stippled box. Conserved glycosylation sites (NXT) are indicated by asterisks. The relative positions of introns in the corresponding genes are shown by triangles. The sequence that was used for the preparation of the zinc-binding GST fusion protein is underlined. The accession numbers are: FishA (Takifugu rubripes A) BN000669, FishB (Takifugu rubripes B) BN000670, Chicken AJ535114, Frog (Silurana tropicalis) AJ616852, Human AJ277437, Mouse AJ293947, Lancelet (Branchiostoma floridae) AJ888866, Sea Urchin (Strongylocentrotus purpuratus) FN252817, Sea Squirt (Ciona intestinalis) XP_002125836. From the sea squirt sequence only the conserved domain (residues 112-456) is included.
Mentions: The three Ig-like domains were aligned with the FGFRL1 sequences from five vertebrates and lancelet (Fig. 1). In the resulting multiple sequence alignment, all the cysteine residues that participate in disulfide-bond formation of the three Ig-like loops are conserved. In contrast, the attachment sites for asparagine-linked carbohydrates are not conserved. The C. intestinalis sequence contains a total of 7 glycosylation signals (NXT/S) from which only two match glycosylation sites in the vertebrate sequences.

Bottom Line: FGFRL1, the gene for the fifth member of the fibroblast growth factor receptor (FGFR) family, is found in all vertebrates from fish to man and in the cephalochordate amphioxus.Since it does not occur in more distantly related invertebrates such as insects and nematodes, we have speculated that FGFRL1 might have evolved just before branching of the vertebrate lineage from the other invertebrates (Beyeler and Trueb, 2006).A comparison of the intracellular domain between sea urchin and human FGFRL1 provides interesting insights into the shaping of a novel zinc binding domain.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Research, University of Bern, 3010 Bern, Switzerland. lei.zhuang@dkf.unibe.ch

ABSTRACT

Background: FGFRL1, the gene for the fifth member of the fibroblast growth factor receptor (FGFR) family, is found in all vertebrates from fish to man and in the cephalochordate amphioxus. Since it does not occur in more distantly related invertebrates such as insects and nematodes, we have speculated that FGFRL1 might have evolved just before branching of the vertebrate lineage from the other invertebrates (Beyeler and Trueb, 2006).

Results: We identified the gene for FGFRL1 also in the sea urchin Strongylocentrotus purpuratus and cloned its mRNA. The deduced amino acid sequence shares 62% sequence similarity with the human protein and shows conservation of all disulfides and N-linked carbohydrate attachment sites. Similar to the human protein, the S. purpuratus protein contains a histidine-rich motif at the C-terminus, but this motif is much shorter than the human counterpart. To analyze the function of the novel motif, recombinant fusion proteins were prepared in a bacterial expression system. The human fusion protein bound to nickel and zinc affinity columns, whereas the sea urchin protein barely interacted with such columns. Direct determination of metal ions by atomic absorption revealed 2.6 mole zinc/mole protein for human FGFRL1 and 1.7 mole zinc/mole protein for sea urchin FGFRL1.

Conclusion: The FGFRL1 gene has evolved much earlier than previously assumed. A comparison of the intracellular domain between sea urchin and human FGFRL1 provides interesting insights into the shaping of a novel zinc binding domain.

Show MeSH
Related in: MedlinePlus