Limits...
The evolution of extracellular fibrillins and their functional domains.

Piha-Gossack A, Sossin W, Reinhardt DP - PLoS ONE (2012)

Bottom Line: Beginning with a single fibrillin sequence found in invertebrates and jawless fish, a gene duplication event, which coincides with the appearance of elastin, led to the creation of two genes.The proline-rich domain in fibrillin-1, glycine-rich domain in fibrillin-2 and proline-/glycine-rich domain in fibrillin-3 are found in all analyzed tetrapod species, whereas it is completely replaced with an EGF-like domain in cnidarians, arthropods, molluscs and urochordates.Furin cleavage sites within the N- and C-terminal unique domains were found for all analyzed fibrillin sequences, indicating an essential role for processing of the fibrillin pro-proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.

ABSTRACT
Fibrillins constitute the major backbone of multifunctional microfibrils in elastic and non-elastic extracellular matrices, and are known to interact with several binding partners including tropoelastin and integrins. Here, we study the evolution of fibrillin proteins. Following sequence collection from 39 organisms representative of the major evolutionary groups, molecular evolutionary genetics and phylogeny inference software were used to generate a series of evolutionary trees using distance-based and maximum likelihood methods. The resulting trees support the concept of gene duplication as a means of generating the three vertebrate fibrillins. Beginning with a single fibrillin sequence found in invertebrates and jawless fish, a gene duplication event, which coincides with the appearance of elastin, led to the creation of two genes. One of the genes significantly evolved to become the gene for present-day fibrillin-1, while the other underwent evolutionary changes, including a second duplication, to produce present-day fibrillin-2 and fibrillin-3. Detailed analysis of several sequences and domains within the fibrillins reveals distinct similarities and differences across various species. The RGD integrin-binding site in TB4 of all fibrillins is conserved in cephalochordates and vertebrates, while the integrin-binding site within cbEGF18 of fibrillin-3 is a recent evolutionary change. The proline-rich domain in fibrillin-1, glycine-rich domain in fibrillin-2 and proline-/glycine-rich domain in fibrillin-3 are found in all analyzed tetrapod species, whereas it is completely replaced with an EGF-like domain in cnidarians, arthropods, molluscs and urochordates. All collected sequences contain the first 9-cysteine hybrid domain, and the second 8-cysteine hybrid domain with exception of arthropods containing an atypical 10-cysteine hybrid domain 2. Furin cleavage sites within the N- and C-terminal unique domains were found for all analyzed fibrillin sequences, indicating an essential role for processing of the fibrillin pro-proteins. The four cysteines in the unique N-terminus and the two cysteines in the unique C-terminus are also highly conserved.

Show MeSH
Overview of the domain structure of the human fibrillin family.Numbers above cbEGF domains and within TB and hybrid domains indicate the relative number of the respective domain within the human fibrillin molecule. RGD sites, proprotein processing sites in the unique N- and C-terminal domains (arrows) and predicted N-glycosylation sites (inverted Y symbols) are indicated.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3306419&req=5

pone-0033560-g001: Overview of the domain structure of the human fibrillin family.Numbers above cbEGF domains and within TB and hybrid domains indicate the relative number of the respective domain within the human fibrillin molecule. RGD sites, proprotein processing sites in the unique N- and C-terminal domains (arrows) and predicted N-glycosylation sites (inverted Y symbols) are indicated.

Mentions: Most of the important structural and functional properties in fibrillins were identified and described with fibrillin nucleotide and protein sequences from mammalian organisms, in particular humans. Thus, the following introductory description of fibrillin properties refers primarily to information available on human fibrillins. The fibrillin family consists of three homologous isoforms, fibrillin-1, -2 and -3. Fibrillins are composed of a typical sequence of individual domains containing between 40–80 amino acid residues (Fig. 1). This characteristic domain signature is 100% conserved between all three fibrillins of mammalian organisms with the exception of an alternatively spliced domain at the N-terminus of fibrillin-3 [17]. Almost all of the fibrillin domains are characterized by a typical number of cysteine residues ranging between 6–9 cysteine residues per domain. Generally, fibrillins are the extracellular proteins with the highest content of cysteine residues (12–13%) [18].


The evolution of extracellular fibrillins and their functional domains.

Piha-Gossack A, Sossin W, Reinhardt DP - PLoS ONE (2012)

Overview of the domain structure of the human fibrillin family.Numbers above cbEGF domains and within TB and hybrid domains indicate the relative number of the respective domain within the human fibrillin molecule. RGD sites, proprotein processing sites in the unique N- and C-terminal domains (arrows) and predicted N-glycosylation sites (inverted Y symbols) are indicated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3306419&req=5

pone-0033560-g001: Overview of the domain structure of the human fibrillin family.Numbers above cbEGF domains and within TB and hybrid domains indicate the relative number of the respective domain within the human fibrillin molecule. RGD sites, proprotein processing sites in the unique N- and C-terminal domains (arrows) and predicted N-glycosylation sites (inverted Y symbols) are indicated.
Mentions: Most of the important structural and functional properties in fibrillins were identified and described with fibrillin nucleotide and protein sequences from mammalian organisms, in particular humans. Thus, the following introductory description of fibrillin properties refers primarily to information available on human fibrillins. The fibrillin family consists of three homologous isoforms, fibrillin-1, -2 and -3. Fibrillins are composed of a typical sequence of individual domains containing between 40–80 amino acid residues (Fig. 1). This characteristic domain signature is 100% conserved between all three fibrillins of mammalian organisms with the exception of an alternatively spliced domain at the N-terminus of fibrillin-3 [17]. Almost all of the fibrillin domains are characterized by a typical number of cysteine residues ranging between 6–9 cysteine residues per domain. Generally, fibrillins are the extracellular proteins with the highest content of cysteine residues (12–13%) [18].

Bottom Line: Beginning with a single fibrillin sequence found in invertebrates and jawless fish, a gene duplication event, which coincides with the appearance of elastin, led to the creation of two genes.The proline-rich domain in fibrillin-1, glycine-rich domain in fibrillin-2 and proline-/glycine-rich domain in fibrillin-3 are found in all analyzed tetrapod species, whereas it is completely replaced with an EGF-like domain in cnidarians, arthropods, molluscs and urochordates.Furin cleavage sites within the N- and C-terminal unique domains were found for all analyzed fibrillin sequences, indicating an essential role for processing of the fibrillin pro-proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.

ABSTRACT
Fibrillins constitute the major backbone of multifunctional microfibrils in elastic and non-elastic extracellular matrices, and are known to interact with several binding partners including tropoelastin and integrins. Here, we study the evolution of fibrillin proteins. Following sequence collection from 39 organisms representative of the major evolutionary groups, molecular evolutionary genetics and phylogeny inference software were used to generate a series of evolutionary trees using distance-based and maximum likelihood methods. The resulting trees support the concept of gene duplication as a means of generating the three vertebrate fibrillins. Beginning with a single fibrillin sequence found in invertebrates and jawless fish, a gene duplication event, which coincides with the appearance of elastin, led to the creation of two genes. One of the genes significantly evolved to become the gene for present-day fibrillin-1, while the other underwent evolutionary changes, including a second duplication, to produce present-day fibrillin-2 and fibrillin-3. Detailed analysis of several sequences and domains within the fibrillins reveals distinct similarities and differences across various species. The RGD integrin-binding site in TB4 of all fibrillins is conserved in cephalochordates and vertebrates, while the integrin-binding site within cbEGF18 of fibrillin-3 is a recent evolutionary change. The proline-rich domain in fibrillin-1, glycine-rich domain in fibrillin-2 and proline-/glycine-rich domain in fibrillin-3 are found in all analyzed tetrapod species, whereas it is completely replaced with an EGF-like domain in cnidarians, arthropods, molluscs and urochordates. All collected sequences contain the first 9-cysteine hybrid domain, and the second 8-cysteine hybrid domain with exception of arthropods containing an atypical 10-cysteine hybrid domain 2. Furin cleavage sites within the N- and C-terminal unique domains were found for all analyzed fibrillin sequences, indicating an essential role for processing of the fibrillin pro-proteins. The four cysteines in the unique N-terminus and the two cysteines in the unique C-terminus are also highly conserved.

Show MeSH