Zhaokai Zhou, Ruiqi Zhang, Aoyang Zhou, Jinxiang Lv, Shuang Chen, Haijiao Zou, Ge Zhang, Ting Lin, Zhan Wang, Yuyuan Zhang, Siyuan Weng, Xinwei Han, Zaoqu Liu
Proteomics appending a complementary dimension to precision oncotherapy
Computational and structural biotechnology journal
pgm1linked congenital disorder glycosylation pgm1cdg autosomal recessive disease characterized several phenotypes lifethreatening research focusing diseaserelated variants dphosphoglucomutase 1 pgm1 protein shown several insoluble vitro expressed low levels patient fibroblasts due observations hypothesized diseaselinked pgm1 protein variants structurally destabilized subject protein quality control pqc rapid intracellular degradation employing yeastbased assays show diseaseassociated human variant pgm1 l516p insoluble inactive highly susceptible ubiquitylation rapid degradation proteasome addition show pgm1 l516p forms aggregates cerevisiae aggregation pattern abundance pgm1 l516p chaperonedependent finally using computational methods perform saturation mutagenesis assess impact possible single residue substitutions pgm1 protein analyses identify numerous missense variants predicted detrimental effects protein function stability suggest many diseaselinked pgm1 variants subject pqclinked degradation silico sitesaturated data set may assist mechanistic interpretation pgm1 variants