ArticlePloS one2011
Biophysical characterization of the olfactomedin domain of myocilin, an extracellular matrix protein implicated in inherited forms of glaucoma.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Myocilin polymorphisms and primary open-angle glaucoma: a systematic review and meta-analysis.PloS one · 2012Pooled it
- Article
- Myocilin misfolding and glaucoma: A 20-year update.Progress in retinal and eye research · 2023Review
- Amyloid fibrillation of the glaucoma associated myocilin protein is inhibited by epicatechin gallate (ECG).RSC advances · 2022Article
- Molecular Insights into Myocilin and Its Glaucoma-Causing Misfolded Olfactomedin Domain Variants.Accounts of chemical research · 2021Review
- An acidic residue buried in the dimer interface of isocitrate dehydrogenase 1 (IDH1) helps regulate catalysis and pH sensitivity.The Biochemical journal · 2020Article
- Molecular Basis of Unexpected Specificity of ABC Transporter-Associated Substrate-Binding Protein DppA from Helicobacter pylori.Journal of bacteriology · 2019Article
- Stable calcium-free myocilin olfactomedin domain variants reveal challenges in differentiating between benign and glaucoma-causing mutations.The Journal of biological chemistry · 2019Article
- Structure and Misfolding of the Flexible Tripartite Coiled-Coil Domain of Glaucoma-Associated Myocilin.Structure (London, England : 1993) · 2017Article
- Enzymatic hydrolysis by transition-metal-dependent nucleophilic aromatic substitution.Nature chemical biology · 2016Article
- Structural basis for misfolding in myocilin-associated glaucoma.Human molecular genetics · 2015Article
- The olfactomedin domain from gliomedin is a β-propeller with unique structural properties.The Journal of biological chemistry · 2015Article
- Molecular Details of Olfactomedin Domains Provide Pathway to Structure-Function Studies.PloS one · 2015Article
- Ligands for glaucoma-associated myocilin discovered by a generic binding assay.ACS chemical biology · 2014Article
- The glaucoma-associated olfactomedin domain of myocilin forms polymorphic fibrils that are constrained by partial unfolding and peptide sequence.Journal of molecular biology · 2014Article
- Design, purification and characterization of a soluble variant of the integral membrane protein MotB for structural studies.Journal of the Royal Society, Interface · 2013Article
- The glaucoma-associated olfactomedin domain of myocilin is a novel calcium binding protein.The Journal of biological chemistry · 2012Article
- Amyloid fibril formation by the glaucoma-associated olfactomedin domain of myocilin.Journal of molecular biology · 2012Article
- Dimerization in the Grb7 protein.Journal of molecular recognition : JMR · 2012Article
- Myocilin, a component of a membrane-associated protein complex driven by a homologous Q-SNARE domain.Biochemistry · 2012Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Myocilin is an eye protein found in the trabecular extracellular matrix (TEM), within the anatomic region that controls fluid flow. Variants of myocilin, localized to its olfactomedin (OLF) domain, have been linked to inherited forms of glaucoma, a disease associated with elevated intraocular pressure. OLF domains have also been implicated in psychiatric diseases and cancers by their involvement in signaling, neuronal growth, and development. However, molecular characterization of OLFs has been hampered by challenges in recombinant expression, a hurdle we have recently overcome for the myocilin OLF domain (myoc-OLF). Here, we report the first detailed solution biophysical characterization of myoc-OLF to gain insight into its structure and function. Myoc-OLF is stable in the presence of glycosaminoglycans, as well as in a wide pH range in buffers with functional groups reminiscent of such glycosaminoglycans. Circular dichroism (CD) reveals significant β-sheet and β-turn secondary structure. Unexpectedly, the CD signature is reminiscent of α-chymotrypsin as well as another ocular protein family, the βγ-crystallins. At neutral pH, intrinsic tryptophan fluorescence and CD melts indicate a highly cooperative transition with a melting temperature of ∼55 °C. Limited proteolysis combined with mass spectrometry reveals that the compact core structural domain of OLF consists of approximately residues 238-461, which retains the single disulfide bond and is as stable as the full myoc-OLF construct. The data presented here inform new testable hypotheses for interactions with specific TEM components, and will assist in design of therapeutic agents for myocilin glaucoma.
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