Structural Analysis of the Effect of Asn107Ser Mutation on Alg13 Activity and Alg13-Alg14 Complex Formation and Expanding the Phenotypic Variability of ALG13-CDG

被引:3
|
作者
Mitusinska, Karolina [1 ]
Gora, Artur [1 ]
Bogdanska, Anna [2 ]
Rozdzynska-Swiatkowska, Agnieszka [3 ]
Tylki-Szymanska, Anna [4 ]
Jezela-Stanek, Aleksandra [5 ]
机构
[1] Silesian Tech Univ, Biotechnol Ctr, Tunneling Grp, PL-44100 Gliwice, Poland
[2] Childrens Mem Hlth Inst, Dept Biochem Radioimmunol & Expt Med, PL-04736 Warsaw, Poland
[3] Childrens Mem Hlth Inst, Anthropol Lab, PL-04736 Warsaw, Poland
[4] Childrens Mem Hlth Inst, Dept Pediat Nutr & Metab Disorders, PL-04736 Warsaw, Poland
[5] Natl Inst TB & Lung Dis, Dept Genet & Clin Immunol, PL-01138 Warsaw, Poland
关键词
ALG13-CDG; c.320A > G variant (p.Asn107Ser); congenital disorder of glycosylation; transferrin isoelectric focusing; human Alg13 modeling; CONGENITAL DISORDERS; PROTEIN-STRUCTURE; GLYCOSYLATION; TRANSFERASE; EXPRESSION; PREDICTION; 2ND-STEP; SEIZURES; VARIANT; SERVER;
D O I
10.3390/biom12030398
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Congenital Disorders of Glycosylation (CDG) are multisystemic metabolic disorders showing highly heterogeneous clinical presentation, molecular etiology, and laboratory results. Here, we present different transferrin isoform patterns (obtained by isoelectric focusing) from three female patients harboring the ALG13 c.320A>G mutation. Contrary to other known variants of type I CDGs, where transferrin isoelectric focusing revealed notably increased asialo- and disialotransferrin fractions, a normal glycosylation pattern was observed in the probands. To verify this data and give novel insight into this variant, we modeled the human Alg13 protein and analyzed the dynamics of the apo structure and the complex with the UDP-GlcNAc substrate. We also modeled the Alg13-Alg14 heterodimer and ran multiple simulations of the complex in the presence of the substrate. Finally, we proposed a plausible complex formation mechanism.
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页数:21
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