View source for Carbohydrate Binding Module Family 47


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* [[Author]]: [[User:Wenwen Tao|Wenwen Tao]]
* [[Responsible Curator]]:  [[User:Yaoguang Chang|Yaoguang Chang]]
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== Ligand specificities ==
The characterization of the C-terminal triplet fucose-binding module (SpX-1.2.3) of protein toxin Sp[[GH98]], originating from the fucose utilization operon in ''Streptococcus pneumoniae'', first defined the CBM47 family <cite>Boraston2006</cite>. ''Anguilla anguilla'' agglutinin (AAA), derived from the European eel, which was characterized earlier and is also classified as an F-type lectin <cite>Bianchet2002</cite>, is also included in the CBM47 family. Several other members of the CBM47 family, such as MsaFBP32 <cite>Bianchet2010</cite>, LLY<Sup>lec</Sup> <cite>Feil2012</cite> and its mutant LLY<Sup>lec</Sup>Y62H <cite>Lawrence2012</cite>, have been confirmed to possess the F-type lectin fold. The aforementioned proteins are all capable of binding to glycans containing fucose, often trisaccharides or smaller, such as the AAA, and a portion of CBM47 members have demonstrated binding to glycans containing galactose <cite>Bianchet2002</cite>. Both of these sugars are ubiquitous in glycoproteins and glycolipids on the cell surface, playing crucial roles in cellular bioactivity and functions. Furthermore, the CBM47 family exhibits specific binding to Lewis blood group oligosaccharides, which are characterized by fucosylation modifications. For instance, LLY<Sup>lec</Sup> binds to both Lewis y (Le<Sup>y</Sup>) antigen (type 1 antigen) and Lewis b (Le<Sup>b</Sup>) antigen (type 2 antigen) <cite>Feil2012</cite>, whereas AAA displays a preference for binding to the Le<Sup>y</Sup> antigen <cite>Bianchet2002</cite>. Consequently, the CBM47 family holds potential applications in immune recognition and disease diagnosis. A novel CBM47 domain was discovered from the marine bacterium ''Wenyingzhuangia fucanilytica'', which is appended to the [[GH168]] family sequence. The CBM exhibited specific binding to sulfated fucans with the backbone composed of 1,3-α-L-fucopyranose residues <cite>Mei2022</cite>.

== Structural Features ==
[[File:CBM47_Fig.1.png|thumb|350px|right|'''Figure 1. Crystal structure of (A) AAA and (B) SpX-1.''' The strand, helix, loop, Ca<sup>2+</sup> and Cl<sup>-</sup> were colored in cyan, yellow, white ,green and origin respectively.]]
The core structures of the CBM47 family exhibit remarkable similarity, adopting an eight-stranded β-sandwich fold, which is comprised of a five-stranded anti-parallel β-sheet on one side and a three-stranded anti-parallel β-sheet on the other <cite>Boraston2006 Bianchet2002 Bianchet2010 Feil2012 Lawrence2012</cite>. Additionally, CBM47 typically exists as a dimer or trimer under physiological conditions, with Ca<sup>2+</sup> playing a pivotal role in maintaining its conformational stability. The CBM47 family recognizes and binds polysaccharides through shallow grooves located within their complementarity-determining regions (CDRs), and these variable loops have been shown to exhibit a high degree of sequence and conformational variability among different CBM47s, enabling them to recognize diverse ligands. For instance, LLY<sup>lec</sup> and SpX-1 reveal smaller differences among their loops, permitting them to bind to a wide array of Lewis blood group oligosaccharides <cite>Boraston2006 Feil2012</cite>. While AAA features a particularly longer and rigid loop, which may account for its preference to form complexes with type 1 antigens while lacking affinity for type 2 antigens <cite>Bianchet2002</cite>. Polysaccharide binding via loop regions typically tends to be of shorter length. 

== Functionalities == 
The AAA, discovered in the serum of European eel, and MsaFBP32, isolated from the plasma of the striped bass ''Morone saxatilis'', participate in the recognition of bacterial lipopolysaccharides by the animal innate immune system <cite>Bianchet2002 Bianchet2010</cite>.

Both LLY<sup>lec</sup> and SpX-1.2.3 are associated with bacterial toxins belonging to [[GH98]] family. Under physiological conditions, these proteins form aggregates that bind to glycoproteins or glycolipids on the cell membrane and insert into the membrane, thereby enhancing the pore-forming activity of the toxins and accelerating cell lysis. Based on the binding specificity to fucoidan, the fluorescein isothiocyanate-labeled SpX-1.2.3 triplet was applied for in situ visualization of mouse lung tissue sections <cite>Boraston2006 Feil2012</cite>.

Sulfated fucans, constituting a pivotal structural component within the body wall of sea cucumbers, are important to the overall architecture and quality of these marine invertebrates. To evaluate the feasibility of WfCBM47 as a tool in the ''in situ'' investigation of sulfated fucan, a fluorescent probe was constructed by fusing WfCBM47 with a green fluorescent protein. The ''in situ'' visualization of sulfated fucan in the sea cucumber (''Apostichopus japonicus'') body wall was implemented for the first time by utilizing the probe <cite>Mei2022</cite>.

== Family Firsts ==
;First Identified:SpX-1.2.3, isolated from ''Streptococcus pneumoniae'' and associated with the toxin SpGH98, was reported in 2006 and was initially proposed to constitute a member of the CBM47 family <cite>Boraston2006</cite>. However, F-type lectin AAA, discovered in the serum of European eel and reported in 2002, has also been included in the CBM47 family by CAZy database <cite>Bianchet2002</cite>.
;First Structural Characterization:All the fucose-binding proteins, SpX-1 ([{{PDBlink}}2j1r PDB 2j1r]), SpX-3 ([{{PDBlink}}2j22 PDB 2j22]) and AAA ([{{PDBlink}}1k12 PDB 1k12]), have had their tertiary structures determined through X-ray crystallography <cite>Boraston2006 Bianchet2002</cite>.

== References ==
<biblio>
#Boraston2006 pmid=16987809
#Bianchet2002 pmid=12091873
#Bianchet2010 pmid=20561530
#Feil2012 pmid=22325774
#Lawrence2012 pmid=23181061
#Mei2022 pmid=34893209
</biblio>

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[[Category:Carbohydrate Binding Module Families|CBM047]]
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