Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 592 (4), 586-598

The Unique Evolution of the Carbohydrate-Binding Module CBM20 in Laforin

Affiliations

The Unique Evolution of the Carbohydrate-Binding Module CBM20 in Laforin

Andrea Kuchtová et al. FEBS Lett.

Abstract

Laforin catalyses glycogen dephosphorylation. Mutations in its gene result in Lafora disease, a fatal progressive myoclonus epilepsy, the hallmark being water-insoluble, hyperphosphorylated carbohydrate inclusions called Lafora bodies. Human laforin consists of an N-terminal carbohydrate-binding module (CBM) from family CBM20 and a C-terminal dual-specificity phosphatase domain. Laforin is conserved in all vertebrates, some basal metazoans and a small group of protozoans. The present in silico study defines the evolutionary relationships among the CBM20s of laforin with an emphasis on newly identified laforin orthologues. The study reveals putative laforin orthologues in Trichinella, a parasitic nematode, and identifies two sequence inserts in the CBM20 of laforin from parasitic coccidia. Finally, we identify that the putative laforin orthologues from some protozoa and algae possess more than one CBM20.

Keywords: Lafora disease; carbohydrate-binding module; domain arrangement; evolutionary relatedness; family CBM20; laforin.

Figures

Fig. 1
Fig. 1
Domain arrangement of human laforin and its representative orthologues. Homo sapiens, Trichinella spiralis and Toxoplasma gondii represent vertebrates, parasitic nematodes and parasitic coccidia, respectively. The non-catalytic CBM20 is in green, whereas the proceeding catalytic DSP is in yellow. The order of the individual CBM20s are numbered from the CBM20 that directly precedes the catalytic DSP (without a number), toward the N-terminus. The CBM20 of laforin from the group of parasitic coccidia, represented by Toxoplasma gondii, contains two amino acid inserts.
Fig. 2
Fig. 2
Amino acid sequence alignment of CBM20s from human laforin and its taxonomically different orthologues. The CBM20 positions involved in starch binding sites 1 and 2 [1,22,45] are signified by numbers “1” and “2”, respectively, below the alignment. The individual residues are coloured as follows: Trp – yellow; Phe, Tyr – red; His – brown; Lys, Arg – cyan; Val, Leu, Ile – blue; Asp, Glu – green; Asp, Gln – dark yellow; Cys – magenta; Met - purple; Ala, Ser, Thr – gray; Gly, Pro – black. The green and red lanes above the alignment discriminate the borders of CBM20 segments (green) from two inserts (red) present in sequences from parasitic coccidia. For details concerning the studied sequences and their colouring scheme, please see Table 1. The individual laforins are marked by the binomial name of the organism preceded by the accession number from the UniProt database (except for the cnidarian Exaiptasia pallida preceded by the GenBank accession number). If there are more CBM20 copies in a single laforin sequence, there are digits “1” and eventually “2” following the accession number from the database. The order of the individual CBM20s is numbered from the CBM20, which directly precedes the catalytic DSP (without a number), toward the N-terminus.
Fig. 3
Fig. 3
Evolutionary tree of (a) laforin CBM20s and (b) laforin DSP domains. The trees are based on the alignment of all laforin CBM20 and DSP sequences from Figure 2 and Table 1.

Similar articles

See all similar articles

Cited by 2 articles

Publication types

MeSH terms

Substances

Associated data

Feedback