ArticleNature structural & molecular biology2021
Cryo-EM structures of human GMPPA-GMPPB complex reveal how cells maintain GDP-mannose homeostasis.
Article in Nature structural & molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Intestinal Fucosylation: A Key Regulatory Hub in Homeostasis and Disease Pathogenesis.Biomolecules · 2026Review
- Gmppb-mutant mice exhibit dystroglycanopathy symptoms that are rescued with GSK3β inhibition or AAV-mediated GMPPB gene replacement.Nature communications · 2026Article
- Proteomic compensation by paralogs preserves protein interaction networks after gene loss in cancer.Molecular systems biology · 2025Article
- A GDP-mannose-1-phosphate guanylyltransferase as a potential HIGS target against Sclerotinia sclerotiorum.PLoS pathogens · 2025Article
- Proteome-wide association studies have predicted that the protein abundance of LSM6, GMPPB, ICA1L, and CISD2 is associated with attention-deficit/hyperactivity disorder.European child & adolescent psychiatry · 2025Article
- Article
- TBC1D23 mediates Golgi-specific LKB1 signaling.Nature communications · 2024Article
- Investigating the shared genetic architecture of osteoarthritis and frailty: a genome-wide cross-trait analysis.American journal of nuclear medicine and molecular imaging · 2024Article
- Ubiquitination contributes to the regulation of GDP-mannose pyrophosphorylase B activity.Frontiers in molecular neuroscience · 2024Article
- Consequences of GMPPB deficiency for neuromuscular development and maintenance.Frontiers in molecular neuroscience · 2024Article
- FAM91A1-TBC1D23 complex structure reveals human genetic variations susceptible for PCH.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structural and Functional Insights into the Stealth Protein CpsY ofBiomolecules · 2023Article
- Silencing GMPPB Inhibits the Proliferation and Invasion of GBM via Hippo/MMP3 Pathways.International journal of molecular sciences · 2023Article
- Systematic Assessment of Protein C-Termini Mutated in Human Disorders.Biomolecules · 2023Article
- Impact of Hypermannosylation on the Structure and Functionality of the ER and the Golgi Complex.Biomedicines · 2023Article
- SCGN deficiency is a risk factor for autism spectrum disorder.Signal transduction and targeted therapy · 2023Article
- Genome-wide identification and expression analysis of GDP-D-mannose pyrophosphorylase and KATANIN inFrontiers in plant science · 2023Article
- Structural insights into selective inhibition of leishmanial GDP-mannose pyrophosphorylase.Cell discovery · 2022Article
- Structures of the mannose-6-phosphate pathway enzyme, GlcNAc-1-phosphotransferase.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- A rare cause of infantile achalasia: GMPPA-congenital disorder of glycosylation with two novel compound heterozygous variants.American journal of medical genetics. Part A · 2022Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GDP-mannose (GDP-Man) is a key metabolite essential for protein glycosylation and glycophosphatidylinositol anchor synthesis, and aberrant cellular GDP-Man levels have been associated with multiple human diseases. How cells maintain homeostasis of GDP-Man is unknown. Here, we report the cryo-EM structures of human GMPPA-GMPPB complex, the protein machinery responsible for GDP-Man synthesis, in complex with GDP-Man or GTP. Unexpectedly, we find that the catalytically inactive subunit GMPPA displays a much higher affinity to GDP-Man than the active subunit GMPPB and, subsequently, inhibits the catalytic activity of GMPPB through a unique C-terminal loop of GMPPA. Importantly, disruption of the interactions between GMPPA and GMPPB or the binding of GDP-Man to GMPPA in zebrafish leads to abnormal brain development and muscle abnormality, analogous to phenotypes observed in individuals carrying GMPPA or GMPPB mutations. We conclude that GMPPA acts as a cellular sensor to maintain mannose homeostasis through allosterically regulating GMPPB.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.