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Molecular Details of Olfactomedin Domains Provide Pathway to Structure-Function Studies.

Hill SE, Donegan RK, Nguyen E, Desai TM, Lieberman RL
PLoS One 10 e0130888 (2015)
Cited: 16 times
EuropePMC logo PMID: 26121352

Abstract

Olfactomedin (OLF) domains are found within extracellular, multidomain proteins in numerous tissues of multicellular organisms. Even though these proteins have been implicated in human disorders ranging from cancers to attention deficit disorder to glaucoma, little is known about their structure(s) and function(s). Here we biophysically, biochemically, and structurally characterize OLF domains from H. sapiens olfactomedin-1 (npoh-OLF, also called noelin, pancortin, OLFM1, and hOlfA), and M. musculus gliomedin (glio-OLF, also called collomin, collmin, and CRG-L2), and compare them with available structures of myocilin (myoc-OLF) recently reported by us and R. norvegicus glio-OLF and M. musculus latrophilin-3 (lat3-OLF) by others. Although the five-bladed β-propeller architecture remains unchanged, numerous physicochemical characteristics differ among these OLF domains. First, npoh-OLF and glio-OLF exhibit prominent, yet distinct, positive surface charges and copurify with polynucleotides. Second, whereas npoh-OLF and myoc-OLF exhibit thermal stabilities typical of human proteins near 55°C, and most myoc-OLF variants are destabilized and highly prone to aggregation, glio-OLF is nearly 20°C more stable and significantly more resistant to chemical denaturation. Phylogenetically, glio-OLF is most similar to primitive OLFs, and structurally, glio-OLF is missing distinguishing features seen in OLFs such as the disulfide bond formed by N- and C- terminal cysteines, the sequestered Ca2+ ion within the propeller central hydrophilic cavity, and a key loop-stabilizing cation-π interaction on the top face of npoh-OLF and myoc-OLF. While deciphering the explicit biological functions, ligands, and binding partners for OLF domains will likely continue to be a challenging long-term experimental pursuit, we used structural insights gained here to generate a new antibody selective for myoc-OLF over npoh-OLF and glio-OLF as a first step in overcoming the impasse in detailed functional characterization of these biomedically important protein domains.

Articles - 4xat mentioned but not cited (4)

  1. Molecular Details of Olfactomedin Domains Provide Pathway to Structure-Function Studies. Hill SE, Donegan RK, Nguyen E, Desai TM, Lieberman RL. PLoS One 10 e0130888 (2015)
  2. In Silico Prediction of Protein Adsorption Energy on Titanium Dioxide and Gold Nanoparticles. Alsharif SA, Power D, Rouse I, Lobaskin V. Nanomaterials (Basel) 10 E1967 (2020)
  3. Calcium-ligand variants of the myocilin olfactomedin propeller selected from invertebrate phyla reveal cross-talk with N-terminal blade and surface helices. Hill SE, Cho H, Raut P, Lieberman RL. Acta Crystallogr D Struct Biol 75 817-824 (2019)
  4. Design and structural characterisation of olfactomedin-1 variants as tools for functional studies. Pronker MF, van den Hoek H, Janssen BJC. BMC Mol Cell Biol 20 50 (2019)


Reviews citing this publication (2)

  1. Advances with Long Non-Coding RNAs in Alzheimer's Disease as Peripheral Biomarker. Garofalo M, Pandini C, Sproviero D, Pansarasa O, Cereda C, Gagliardi S. Genes (Basel) 12 (2021)
  2. Myocilin misfolding and glaucoma: A 20-year update. Saccuzzo EG, Youngblood HA, Lieberman RL. Prog Retin Eye Res 95 101188 (2023)

Articles citing this publication (10)

  1. Automated Structure- and Sequence-Based Design of Proteins for High Bacterial Expression and Stability. Goldenzweig A, Goldsmith M, Hill SE, Gertman O, Laurino P, Ashani Y, Dym O, Unger T, Albeck S, Prilusky J, Lieberman RL, Aharoni A, Silman I, Sussman JL, Tawfik DS, Fleishman SJ. Mol Cell 63 337-346 (2016)
  2. Structure and Misfolding of the Flexible Tripartite Coiled-Coil Domain of Glaucoma-Associated Myocilin. Hill SE, Nguyen E, Donegan RK, Patterson-Orazem AC, Hazel A, Gumbart JC, Lieberman RL. Structure 25 1697-1707.e5 (2017)
  3. A blueprint for academic laboratories to produce SARS-CoV-2 quantitative RT-PCR test kits. Mascuch SJ, Fakhretaha-Aval S, Bowman JC, Ma MTH, Thomas G, Bommarius B, Ito C, Zhao L, Newnam GP, Matange KR, Thapa HR, Barlow B, Donegan RK, Nguyen NA, Saccuzzo EG, Obianyor CT, Karunakaran SC, Pollet P, Rothschild-Mancinelli B, Mestre-Fos S, Guth-Metzler R, Bryksin AV, Petrov AS, Hazell M, Ibberson CB, Penev PI, Mannino RG, Lam WA, Garcia AJ, Kubanek J, Agarwal V, Hud NV, Glass JB, Williams LD, Lieberman RL. J Biol Chem 295 15438-15453 (2020)
  4. Binding of a glaucoma-associated myocilin variant to the αB-crystallin chaperone impedes protein clearance in trabecular meshwork cells. Lynch JM, Li B, Katoli P, Xiang C, Leehy B, Rangaswamy N, Saenz-Vash V, Wang YK, Lei H, Nicholson TB, Meredith E, Rice DS, Prasanna G, Chen A. J Biol Chem 293 20137-20156 (2018)
  5. Differential Misfolding Properties of Glaucoma-Associated Olfactomedin Domains from Humans and Mice. Patterson-Orazem AC, Hill SE, Wang Y, Dominic IM, Hall CK, Lieberman RL. Biochemistry 58 1718-1727 (2019)
  6. Epitope mapping of commercial antibodies that detect myocilin. Patterson-Orazem AC, Hill SE, Fautsch MP, Lieberman RL. Exp Eye Res 173 109-112 (2018)
  7. Stable calcium-free myocilin olfactomedin domain variants reveal challenges in differentiating between benign and glaucoma-causing mutations. Hill SE, Kwon MS, Martin MD, Suntharalingam A, Hazel A, Dickey CA, Gumbart JC, Lieberman RL. J Biol Chem 294 12717-12728 (2019)
  8. Pocket detection and interaction-weighted ligand-similarity search yields novel high-affinity binders for Myocilin-OLF, a protein implicated in glaucoma. Srinivasan B, Tonddast-Navaei S, Skolnick J. Bioorg Med Chem Lett 27 4133-4139 (2017)
  9. Calcium dysregulation potentiates wild-type myocilin misfolding: implications for glaucoma pathogenesis. Saccuzzo EG, Martin MD, Hill KR, Ma MT, Ku Y, Lieberman RL. J Biol Inorg Chem 27 553-564 (2022)
  10. Structure‒function‒pathogenicity analysis of C-terminal myocilin missense variants based on experiments and 3D models. Zhou B, Lin X, Li Z, Yao Y, Yang J, Zhu Y. Front Genet 13 1019208 (2022)


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