The vertebrate sialylation machinery: structure-function and molecular evolution of GT-29 sialyltransferases

Harduin-Lepers, Anne

doi:10.1007/s10719-023-10123-w

Cited by 8 publications

(6 citation statements)

References 176 publications

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“…Sialic acids are found prominently expressed in deuterostomes and almost absent in the protostome lineage ( 47 ). In accordance with this, sialyltransferases, the enzymes that add sialic acid resides to nascent glycans, are only present as a large gene family in deuterostomes ( 48 ). It is speculated that the sialylation machinery evolved in the last common ancestor of metazoa before the separation of protostomes and deuterostomes.…”

Section: Resultsmentioning

confidence: 83%

A brief history of galectin evolution

Günther

Galuska

2023

Front. Immunol.

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Galectins are a family of carbohydrate-binding proteins found in vertebrates in great abundance and diversity in terms of both structure and ligand-binding properties as well as physiological function. Proteins with clear relationships to vertebrate galectins are already found in primitive Bilateria. The increasing amount of accessible well-annotated bilaterian genomes has allowed us to reveal, through synteny analyses, a new hypothesis about the phylogenetic history of the galectin family in this animal group. Thus, we can trace the genomic localization of the putative ancestral Bilateria galectin back to the scallops as a still very primitive slow-evolving bilaterian lineage. Intriguingly, our analyses show that the primordial galectin of the Deuterostomata most likely exhibited galectin-8-like characteristics. This basal standing galectin is characterized by a tandem-repeat type with two carbohydrate recognition domains as well as by a sialic acid binding property of the N-terminal domain, which is typical for galectin-8. With the help of synteny, the amplification of this potential primordial galectin to the broad galectin cosmos of modern jawed vertebrates can be reconstructed. Therefore, it is possible to distinguish between the paralogs resulting from small-scale duplication and the ohnologues generated by whole-genome duplication. Our findings support a substantially new hypothesis about the origin of the various members of the galectin family in vertebrates. This allows us to reveal new theories on the kinship relationships of the galectins of Gnatostomata. In addition, we focus for the first time on the galectines of the Cyclostomata, which as a sister group of jawed vertebrates providing important insights into the evolutionary history of the entire subphylum. Our studies also highlight a previously neglected member of the galectin family, galectin-related protein 2. This protein appears to be a widespread ohnologue of the original tandem-repeat ancestor within Gnathostomata that has not been the focus of galectin research due to its nonclassical galactose binding sequence motif and the fact that it was lost during mammalian evolution.

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Section: Resultsmentioning

confidence: 83%

A brief history of galectin evolution

Günther

Galuska

2023

Front. Immunol.

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“…To date, several common structural motifs important for the ST activity have been demonstrated to be involved in the donor substrate CMP-Sia binding and/or the acceptor–substrate recognition ( 2 ). These motifs were first proposed based on the conserved AA sequences among STs and then biochemically characterized for the role in the enzyme reaction by their point mutations and subsequent evaluation of the catalytic activity.…”

Section: Discussionmentioning

confidence: 99%

“…Sialic acid (Sia) forms glycan epitopes essential for many biological functions including embryogenesis, fertilization, development, and the immune and nervous systems ( 1 ). The expression of Sia-glycan epitopes is highly regulated by synthetic enzymes known as sialyltransferases (STs), and the impairment of Sia expression has been reported to be related to diseases such as infection, cancer, and mental disorders ( 2 ). Among Sia epitopes, polysialic acid (polySia), a polymer of Sia, is a well-known development- and disease-related epitope ( 3 ).…”

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confidence: 99%

“…Notably, the domain structures of these enzymes are highly conserved: they consist of a very short cytoplasmic region, a transmembrane region, a stem region, and a catalytic domain in the intraluminal region. The catalytic region consists of sialyl motifs L, S, III, and VS, which are common in α2,3-, α2,6-, and α2,8-sialyltransferases of the CAZy GT29 family ( 2 ). Although the whole sequence homology was low among STs, these sialyl motifs are highly homologous among them and share the common functional importance: sialyl motif L serves as a binding site for the donor substrate (CMP-Sia); sialyl motif S serves as a binding site for both the donor and acceptor substrates; sialyl motif III is located between sialyl motifs S and VS and is involved in the catalytic activity; and the histidine residue of the sialyl motif VS is involved in the catalytic activity.…”

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confidence: 99%

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Identification of a buried β-strand as a novel disease-related motif in the human polysialyltransferases

Hatanaka,

Hane,

Hayakawa

et al. 2024

Journal of Biological Chemistry

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“…sialyltransferases) catalyzing the transfer of Sia residues from an activated donor substrate CMP-sialic acid (CMP-Sia, Fig. 1 ) onto glycolipids or glycoproteins are classified into ST3GAL, ST6GAL, ST6GALNAC and ST8SIA 20 , 21 . Phylogenetic distribution of sialyltransferases was assessed in Metazoan and found to be extremely diverse in teleost fishes 19 , 22 , 23 .…”

Section: Introductionmentioning

confidence: 99%

Salmonid polysialyltransferases to generate a variety of sialic acid polymers

Decloquement,

Venuto,

Cogez

et al. 2023

Sci Rep

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The human polysialyltransferases ST8Sia II and ST8Sia IV catalyze the transfer of several Neu5Ac residues onto glycoproteins forming homopolymers with essential roles during different physiological processes. In salmonids, heterogeneous set of sialic acids polymers have been described in ovary and on eggs cell surface and three genes st8sia4, st8sia2-r1 and st8sia2-r2 were identified that could be implicated in these heteropolymers. The three polysialyltransferases from the salmonid Coregonus maraena were cloned, recombinantly expressed in HEK293 cells and the ST8Sia IV was biochemically characterized. The MicroPlate Sialyltransferase Assay and the non-natural donor substrate CMP-SiaNAl were used to demonstrate enzyme activity and optimize polysialylation reactions. Polysialylation was also carried out with natural donor substrates CMP-Neu5Ac, CMP-Neu5Gc and CMP-Kdn in cell-free and cell-based assays and structural analyses of polysialylated products using the anti-polySia monoclonal antibody 735 and endoneuraminidase N and HPLC approaches. Our data highlighted distinct specificities of human and salmonid polysialyltransferases with notable differences in donor substrates use and the capacity of fish enzymes to generate heteropolymers. This study further suggested an evolution of the biological functions of polySia. C. maraena ST8Sia IV of particular interest to modify glycoproteins with a variety of polySia chains.

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The vertebrate sialylation machinery: structure-function and molecular evolution of GT-29 sialyltransferases

Cited by 8 publications

References 176 publications

A brief history of galectin evolution

A brief history of galectin evolution

Identification of a buried β-strand as a novel disease-related motif in the human polysialyltransferases

Salmonid polysialyltransferases to generate a variety of sialic acid polymers

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