ArticleThe Journal of biological chemistry2019
Stable calcium-free myocilin olfactomedin domain variants reveal challenges in differentiating between benign and glaucoma-causing mutations.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- OLFML2A expression in acute myeloid leukemia, with exploratory findings in acute lymphoblastic leukemia: Prognostic significance and re-analysis of public single-cell transcriptomic data.Oncology letters · 2026Article
- GOLF: A Generative AI Framework for Pathogenicity Prediction of Myocilin OLF Variants.bioRxiv : the preprint server for biology · 2025Article
- Article
- Evidence for SbioRxiv : the preprint server for biology · 2024Article
- Competition between inside-out unfolding and pathogenic aggregation in an amyloid-forming β-propeller.Nature communications · 2024Article
- Evaluation of Myocilin Variant Protein Structures Modeled by AlphaFold2.Biomolecules · 2023Article
- Human Pro370Leu Mutant Myocilin Induces the Phenotype of Open-Angle Glaucoma in Transgenic Mice.Cellular and molecular neurobiology · 2023Article
- Myocilin misfolding and glaucoma: A 20-year update.Progress in retinal and eye research · 2023Review
- Quantitative differentiation of benign and misfolded glaucoma-causing myocilin variants on the basis of protein thermal stability.Disease models & mechanisms · 2023Article
- Amyloid fibrillation of the glaucoma associated myocilin protein is inhibited by epicatechin gallate (ECG).RSC advances · 2022Article
- Calcium dysregulation potentiates wild-type myocilin misfolding: implications for glaucoma pathogenesis.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2022Article
- A Simple Secretion Assay for Assessing New and Existing Myocilin Variants.Current eye research · 2022Article
- Common and rare myocilin variants: Predicting glaucoma pathogenicity based on genetics, clinical, and laboratory misfolding data.Human mutation · 2021Review
- A PROSS-designed extensively mutated estrogen receptor α variant displays enhanced thermal stability while retaining native allosteric regulation and structure.Scientific reports · 2021Article
- Molecular Insights into Myocilin and Its Glaucoma-Causing Misfolded Olfactomedin Domain Variants.Accounts of chemical research · 2021Review
- Calcium-ligand variants of the myocilin olfactomedin propeller selected from invertebrate phyla reveal cross-talk with N-terminal blade and surface helices.Acta crystallographica. Section D, Structural biology · 2019Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Nonsynonymous gene mutations can be beneficial, neutral, or detrimental to the stability, structure, and biological function of the encoded protein, but the effects of these mutations are often not readily predictable. For example, the β-propeller olfactomedin domain of myocilin (mOLF) exhibits a complex interrelationship among structure(s), stability, and aggregation. Numerous mutations within mOLF are linked to glaucoma; the resulting variants are less stable, aggregation-prone, and sequestered intracellularly, causing cytotoxicity. Here, we report the first stable mOLF variants carrying substitutions in the calcium-binding site that exhibit solution characteristics indistinguishable from those of glaucoma variants. Crystal structures of these stable variants at 1.8-2.0-Å resolution revealed features that we could not predict by molecular dynamics simulations, including loss of loop structure, helix unwinding, and a blade shift. Double mutants that combined a stabilizing substitution and a selected glaucoma-causing single-point mutant rescued
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Registered trials
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 Socratic graph.