Stable calcium-free myocilin olfactomedin domain variants reveal challenges in differentiating between benign and glaucoma-causing mutations

Hill, Shannon E.; Kwon, Michelle S.; Martin, Mackenzie D.; Suntharalingam, Amirthaa; Hazel, Anthony; Dickey, Chad A.; Gumbart, James C.; Lieberman, Raquel L.

doi:10.1074/jbc.ra119.009419

Stable calcium-free myocilin olfactomedin domain variants reveal challenges in differentiating between benign and glaucoma-causing mutations

Journal Article · Tue Jul 02 00:00:00 EDT 2019 · Journal of Biological Chemistry

DOI:https://doi.org/10.1074/jbc.ra119.009419· OSTI ID:1562708

Hill, Shannon E. ^[1]; ^[1]; Martin, Mackenzie D. ^[1]; Suntharalingam, Amirthaa ^[2]; Hazel, Anthony ^[1]; Dickey, Chad A. ^[2]; ^[1]; ^[1]

Georgia Institute of Technology, Atlanta, GA (United States)
Univ. of South Florida, Tampa, FL (United States)

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. In this study, 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 in vitro folding and stability defects. In the context of full-length myocilin, secretion of stable single variants was indistinguishable from that of the WT protein, and the double mutants were secreted to varying extents. In summary, our finding that mOLF can tolerate particular substitutions that render the protein stable despite a conformational switch emphasizes the complexities in differentiating between benign and glaucoma-causing variants and provides new insight into the possible biological function of myocilin.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE

OSTI ID:: 1562708

Journal Information:: Journal of Biological Chemistry, Journal Name: Journal of Biological Chemistry Journal Issue: 34 Vol. 294; ISSN 0021-9258

Publisher:: American Society for Biochemistry and Molecular BiologyCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (79)

Scalable molecular dynamics with NAMD Phillips, James C.; Braun, Rosemary; Wang, Wei Journal of Computational Chemistry, Vol. 26, Issue 16, p. 1781-1802 https://doi.org/10.1002/jcc.20289	journal	January 2005
NMRPipe: A multidimensional spectral processing system based on UNIX pipes Delaglio, Frank; Grzesiek, Stephan; Vuister, GeertenW. Journal of Biomolecular NMR, Vol. 6, Issue 3 https://doi.org/10.1007/BF00197809	journal	November 1995
Olfactomedin domain-containing proteins: evolution, functional divergence, expression patterns and damaging SNPs Li, Qin; Liu, Ake; Gu, Xun Molecular Genetics and Genomics, Vol. 294, Issue 4 https://doi.org/10.1007/s00438-019-01549-9	journal	March 2019
Improving the specificity of organophosphorus hydrolase to acephate by mutagenesis at its binding site: a computational study Badakhshan, Reza; Mohammadi, Mozafar; Farnoosh, Gholamreza Journal of Molecular Modeling, Vol. 27, Issue 6 https://doi.org/10.1007/s00894-021-04749-6	journal	May 2021
VMD: Visual molecular dynamics Humphrey, William; Dalke, Andrew; Schulten, Klaus Journal of Molecular Graphics, Vol. 14, Issue 1 https://doi.org/10.1016/0263-7855(96)00018-5	journal	February 1996
Evolution of an Antibiotic Resistance Enzyme Constrained by Stability and Activity Trade-offs Wang, Xiaojun; Minasov, George; Shoichet, Brian K. Journal of Molecular Biology, Vol. 320, Issue 1 https://doi.org/10.1016/S0022-2836(02)00400-X	journal	June 2002
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
Stability and function: two constraints in the evolution of barstar and other proteins Schreiber, Gideon; Buckle, Ashley M.; Fersht, Alan R. Structure, Vol. 2, Issue 10 https://doi.org/10.1016/S0969-2126(94)00096-4	journal	October 1994
Reversal of mutant myocilin non-secretion and cell killing: Implications for glaucoma Liu, Y.; Vollrath, D. American Journal of Ophthalmology, Vol. 139, Issue 2 https://doi.org/10.1016/j.ajo.2004.12.036	journal	February 2005
Accumulation of mutant myocilins in ER leads to ER stress and potential cytotoxicity in human trabecular meshwork cells Joe, Myung Kuk; Sohn, Seongsoo; Hur, Wonhee Biochemical and Biophysical Research Communications, Vol. 312, Issue 3 https://doi.org/10.1016/j.bbrc.2003.10.162	journal	December 2003
In vivo folding efficiencies for mutants of the P22 tailspike β-helix protein correlate with predicted stability changes Reich, Lothar; Becker, Marion; Seckler, Robert Biophysical Chemistry, Vol. 141, Issue 2-3 https://doi.org/10.1016/j.bpc.2009.01.015	journal	May 2009
Temperature sensitive secretion of mutant myocilins Vollrath, Douglas; Liu, Yuhui Experimental Eye Research, Vol. 82, Issue 6 https://doi.org/10.1016/j.exer.2005.10.007	journal	June 2006
Mutant human myocilin induces strain specific differences in ocular hypertension and optic nerve damage in mice McDowell, Colleen M.; Luan, Tomi; Zhang, Zhang Experimental Eye Research, Vol. 100 https://doi.org/10.1016/j.exer.2012.04.016	journal	July 2012
Targeting the ER-autophagy system in the trabecular meshwork to treat glaucoma Stothert, Andrew R.; Fontaine, Sarah N.; Sabbagh, Jonathan J. Experimental Eye Research, Vol. 144 https://doi.org/10.1016/j.exer.2015.08.017	journal	March 2016
Elucidation of subfamily segregation and intramolecular coevolution of the olfactomedin-like proteins by comprehensive phylogenetic analysis and gene expression pattern assessment Zeng, Ling-Chun; Han, Ze-Guang; Ma, Wei-Jun FEBS Letters, Vol. 579, Issue 25 https://doi.org/10.1016/j.febslet.2005.08.064	journal	September 2005
Conformational Transitions of Adenylate Kinase: Switching by Cracking Whitford, Paul C.; Miyashita, Osamu; Levy, Yaakov Journal of Molecular Biology, Vol. 366, Issue 5 https://doi.org/10.1016/j.jmb.2006.11.085	journal	March 2007
Correlation of Levels of Folded Recombinant p53 in Escherichia coli with Thermodynamic Stability in Vitro Mayer, Sebastian; Rüdiger, Stefan; Ang, Hwee Ching Journal of Molecular Biology, Vol. 372, Issue 1 https://doi.org/10.1016/j.jmb.2007.06.044	journal	September 2007
Amyloid Fibril Formation by the Glaucoma-Associated Olfactomedin Domain of Myocilin Orwig, Susan D.; Perry, Christopher W.; Kim, Laura Y. Journal of Molecular Biology, Vol. 421, Issue 2-3 https://doi.org/10.1016/j.jmb.2011.12.016	journal	August 2012
The Glaucoma-Associated Olfactomedin Domain of Myocilin Forms Polymorphic Fibrils That Are Constrained by Partial Unfolding and Peptide Sequence Hill, Shannon E.; Donegan, Rebecca K.; Lieberman, Raquel L. Journal of Molecular Biology, Vol. 426, Issue 4 https://doi.org/10.1016/j.jmb.2013.12.002	journal	February 2014
Automated Structure- and Sequence-Based Design of Proteins for High Bacterial Expression and Stability Goldenzweig, Adi; Goldsmith, Moshe; Hill, Shannon E. Molecular Cell, Vol. 63, Issue 2 https://doi.org/10.1016/j.molcel.2016.06.012	journal	July 2016
Automated Structure- and Sequence-Based Design of Proteins for High Bacterial Expression and Stability Goldenzweig, Adi; Goldsmith, Moshe; Hill, Shannon E. Molecular Cell, Vol. 70, Issue 2 https://doi.org/10.1016/j.molcel.2018.03.035	journal	April 2018
Gene–environment interactions in ocular diseases Sacca, S. C.; Bolognesi, C.; Battistella, A. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 667, Issue 1-2 https://doi.org/10.1016/j.mrfmmm.2008.11.002	journal	July 2009
Stability effects of mutations and protein evolvability Tokuriki, Nobuhiko; Tawfik, Dan S. Current Opinion in Structural Biology, Vol. 19, Issue 5 https://doi.org/10.1016/j.sbi.2009.08.003	journal	October 2009
Ensemble Refinement of Protein Crystal Structures: Validation and Application Levin, Elena J.; Kondrashov, Dmitry A.; Wesenberg, Gary E. Structure, Vol. 15, Issue 9 https://doi.org/10.1016/j.str.2007.06.019	journal	September 2007
Helix Cracking Regulates the Critical Interaction between RetS and GacS in Pseudomonas aeruginosa Mancl, Jordan M.; Ray, William K.; Helm, Rich F. Structure, Vol. 27, Issue 5 https://doi.org/10.1016/j.str.2019.02.006	journal	May 2019
Regulated unfolding: a basic principle of intraprotein signaling in modular proteins Schultz, Joachim E.; Natarajan, Janani Trends in Biochemical Sciences, Vol. 38, Issue 11 https://doi.org/10.1016/j.tibs.2013.08.005	journal	November 2013
Biological Roles of Protein Kinetic Stability Colón, Wilfredo; Church, Jennifer; Sen, Jayeeta Biochemistry, Vol. 56, Issue 47 https://doi.org/10.1021/acs.biochem.7b00942	journal	November 2017
Trifunctional High-Throughput Screen Identifies Promising Scaffold To Inhibit Grp94 and Treat Myocilin-Associated Glaucoma Huard, Dustin J. E.; Crowley, Vincent M.; Du, Yuhong ACS Chemical Biology, Vol. 13, Issue 4 https://doi.org/10.1021/acschembio.7b01083	journal	February 2018
The Stability of Myocilin Olfactomedin Domain Variants Provides New Insight into Glaucoma as a Protein Misfolding Disorder Burns, J. Nicole; Turnage, Katherine C.; Walker, Chandler A. Biochemistry, Vol. 50, Issue 26 https://doi.org/10.1021/bi200231x	journal	July 2011
Rescue of Glaucoma-Causing Mutant Myocilin Thermal Stability by Chemical Chaperones Burns, J. Nicole; Orwig, Susan D.; Harris, Julia L. ACS Chemical Biology, Vol. 5, Issue 5 https://doi.org/10.1021/cb900282e	journal	March 2010
Optimization of the Additive CHARMM All-Atom Protein Force Field Targeting Improved Sampling of the Backbone ϕ, ψ and Side-Chain χ ₁ and χ ₂ Dihedral Angles Best, Robert B.; Zhu, Xiao; Shim, Jihyun Journal of Chemical Theory and Computation, Vol. 8, Issue 9 https://doi.org/10.1021/ct300400x	journal	August 2012
Energy landscapes of functional proteins are inherently risky Gershenson, Anne; Gierasch, Lila M.; Pastore, Annalisa Nature Chemical Biology, Vol. 10, Issue 11 https://doi.org/10.1038/nchembio.1670	journal	October 2014
Calcium modulates force sensing by the von Willebrand factor A2 domain Jakobi, Arjen J.; Mashaghi, Alireza; Tans, Sander J. Nature Communications, Vol. 2, Issue 1 https://doi.org/10.1038/ncomms1385	journal	July 2011
Missense meanderings in sequence space: a biophysical view of protein evolution DePristo, Mark A.; Weinreich, Daniel M.; Hartl, Daniel L. Nature Reviews Genetics, Vol. 6, Issue 9 https://doi.org/10.1038/nrg1672	journal	August 2005
Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus Wang, Ning; Tytell, Jessica D.; Ingber, Donald E. Nature Reviews Molecular Cell Biology, Vol. 10, Issue 1 https://doi.org/10.1038/nrm2594	journal	January 2009
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome Sharma, Deepti; De Falco, Louis; Padavattan, Sivaraman Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-13641-0	journal	December 2019
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation Tillu, Vikas A.; Rae, James; Gao, Ya Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-21035-4	journal	February 2021
Isoform-selective Hsp90 inhibition rescues model of hereditary open-angle glaucoma Stothert, Andrew R.; Suntharalingam, Amirthaa; Tang, Xiaolan Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/s41598-017-18344-4	journal	December 2017
Multi-functionality of a tryptophan residue conserved in substrate-binding groove of GH19 chitinases Nagata, Takuya; Shinya, Shoko; Ohnuma, Takayuki Scientific Reports, Vol. 11, Issue 1 https://doi.org/10.1038/s41598-021-81903-3	journal	January 2021
Comparison of simple potential functions for simulating liquid water Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D. The Journal of Chemical Physics, Vol. 79, Issue 2 https://doi.org/10.1063/1.445869	journal	July 1983
Particle mesh Ewald: An N ⋅log( N ) method for Ewald sums in large systems Darden, Tom; York, Darrin; Pedersen, Lee The Journal of Chemical Physics, Vol. 98, Issue 12 https://doi.org/10.1063/1.464397	journal	June 1993
Constant pressure molecular dynamics simulation: The Langevin piston method Feller, Scott E.; Zhang, Yuhong; Pastor, Richard W. The Journal of Chemical Physics, Vol. 103, Issue 11 https://doi.org/10.1063/1.470648	journal	September 1995
Protein stability promotes evolvability Bloom, J. D.; Labthavikul, S. T.; Otey, C. R. Proceedings of the National Academy of Sciences, Vol. 103, Issue 15, p. 5869-5874 https://doi.org/10.1073/pnas.0510098103	journal	March 2006
CRISPR-Cas9–based treatment of myocilin-associated glaucoma Jain, Ankur; Zode, Gulab; Kasetti, Ramesh B. Proceedings of the National Academy of Sciences, Vol. 114, Issue 42 https://doi.org/10.1073/pnas.1706193114	journal	October 2017
A relationship between protein stability and protein function. Shoichet, B. K.; Baase, W. A.; Kuroki, R. Proceedings of the National Academy of Sciences, Vol. 92, Issue 2 https://doi.org/10.1073/pnas.92.2.452	journal	January 1995
Glucose-regulated Protein 94 Triage of Mutant Myocilin through Endoplasmic Reticulum-associated Degradation Subverts a More Efficient Autophagic Clearance Mechanism Suntharalingam, Amirthaa; Abisambra, Jose F.; O'Leary, John C. Journal of Biological Chemistry, Vol. 287, Issue 48 https://doi.org/10.1074/jbc.M112.384800	journal	October 2012
The Glaucoma-associated Olfactomedin Domain of Myocilin Is a Novel Calcium Binding Protein Donegan, Rebecca K.; Hill, Shannon E.; Turnage, Katherine C. Journal of Biological Chemistry, Vol. 287, Issue 52 https://doi.org/10.1074/jbc.M112.408906	journal	November 2012
The Olfactomedin Domain from Gliomedin Is a β-Propeller with Unique Structural Properties Han, Huijong; Kursula, Petri Journal of Biological Chemistry, Vol. 290, Issue 6 https://doi.org/10.1074/jbc.M114.627547	journal	December 2014
Secreted gliomedin is a perinodal matrix component of peripheral nerves Eshed, Yael; Feinberg, Konstantin; Carey, David J. The Journal of Cell Biology, Vol. 177, Issue 3 https://doi.org/10.1083/jcb.200612139	journal	May 2007
Prevalence of Mutations in TIGR/Myocilin in Patients with Adult and Juvenile Primary Open-Angle Glaucoma Wiggs, Janey L.; Allingham, R. Rand; Vollrath, Douglas The American Journal of Human Genetics, Vol. 63, Issue 5 https://doi.org/10.1086/302098	journal	November 1998
Intraocular Pressure Homeostasis: Maintaining Balance in a High-Pressure Environment Acott, Ted S.; Kelley, Mary J.; Keller, Kate E. Journal of Ocular Pharmacology and Therapeutics, Vol. 30, Issue 2-3 https://doi.org/10.1089/jop.2013.0185	journal	March 2014
A Cellular Assay Distinguishes Normal and Mutant TIGR/Myocilin Protein Zhou, Z.; Vollrath, D. Human Molecular Genetics, Vol. 8, Issue 12 https://doi.org/10.1093/hmg/8.12.2221	journal	November 1999
Reversal of mutant myocilin non-secretion and cell killing: implications for glaucoma Liu, Yuhui; Vollrath, Douglas Human Molecular Genetics, Vol. 13, Issue 11 https://doi.org/10.1093/hmg/ddh128	journal	April 2004
Exploiting the interaction between Grp94 and aggregated myocilin to treat glaucoma Stothert, Andrew R.; Suntharalingam, Amirthaa; Huard, Dustin J. E. Human Molecular Genetics, Vol. 23, Issue 24 https://doi.org/10.1093/hmg/ddu367	journal	July 2014
Structural basis for misfolding in myocilin-associated glaucoma Donegan, Rebecca K.; Hill, Shannon E.; Freeman, Dana M. Human Molecular Genetics, Vol. 24, Issue 8 https://doi.org/10.1093/hmg/ddu730	journal	December 2014
Genetics of glaucoma Wiggs, Janey L.; Pasquale, Louis R. Human Molecular Genetics, Vol. 26, Issue R1 https://doi.org/10.1093/hmg/ddx184	journal	May 2017
Prevalence of Myocilin Mutations in Adults with Primary Open-angle Glaucoma in Ghana, West Africa Challa, P.; Herndon, L. W.; Hauser, M. A. Journal of Glaucoma, Vol. 11, Issue 5 https://doi.org/10.1097/00061198-200210000-00008	journal	January 2002
Stress Response of the Trabecular Meshwork Liton, Paloma B.; Gonzalez, Pedro Journal of Glaucoma, Vol. 17, Issue 5 https://doi.org/10.1097/IJG.0b013e31815f52a8	journal	January 2008
The Nodes of Ranvier: Molecular Assembly and Maintenance Rasband, Matthew N.; Peles, Elior Cold Spring Harbor Perspectives in Biology, Vol. 8, Issue 3 https://doi.org/10.1101/cshperspect.a020495	journal	September 2015
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
Towards automated crystallographic structure refinement with phenix.refine Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Echols, Nathaniel Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4 https://doi.org/10.1107/S0907444912001308	journal	March 2012
Protein Dynamism and Evolvability Tokuriki, N.; Tawfik, D. S. Science, Vol. 324, Issue 5924 https://doi.org/10.1126/science.1169375	journal	April 2009
Identification of a Gene That Causes Primary Open Angle Glaucoma Stone, E. M. Science, Vol. 275, Issue 5300 https://doi.org/10.1126/science.275.5300.668	journal	January 1997
In vivo aspects of protein folding and quality control Balchin, David; Hayer-Hartl, Manajit; Hartl, F. Ulrich Science, Vol. 353, Issue 6294 https://doi.org/10.1126/science.aac4354	journal	June 2016
Regulation of Trabecular Meshwork Contractility Stumpff, Friederike; Wiederholt, Michael Ophthalmologica, Vol. 214, Issue 1 https://doi.org/10.1159/000027471	journal	January 2000
Intracellular Sequestration of Hetero-oligomers Formed by Wild-Type and Glaucoma-Causing Myocilin Mutants Gobeil, Ste´phane; Rodrigue, Marc-Andre´; Moisan, Steve Investigative Opthalmology & Visual Science, Vol. 45, Issue 10 https://doi.org/10.1167/iovs.04-0300	journal	October 2004
Extracellular Matrix Gene Alternative Splicing by Trabecular Meshwork Cells in Response to Mechanical Stretching Keller, Kate E.; Kelley, Mary J.; Acott, Ted S. Investigative Opthalmology & Visual Science, Vol. 48, Issue 3 https://doi.org/10.1167/iovs.06-0875	journal	March 2007
The Cell and Molecular Biology of Glaucoma: Biomechanical Factors in Glaucoma Clark, Abbot F. Investigative Opthalmology & Visual Science, Vol. 53, Issue 5 https://doi.org/10.1167/iovs.12-9483g	journal	May 2012
Reduction of ER stress via a chemical chaperone prevents disease phenotypes in a mouse model of primary open angle glaucoma Zode, Gulab S.; Kuehn, Markus H.; Nishimura, Darryl Y. Journal of Clinical Investigation, Vol. 121, Issue 9 https://doi.org/10.1172/JCI58183	journal	September 2011
Reduction of ER stress via a chemical chaperone prevents disease phenotypes in a mouse model of primary open angle glaucoma Zode, Gulab S.; Kuehn, Markus H.; Nishimura, Darryl Y. Journal of Clinical Investigation, Vol. 125, Issue 8 https://doi.org/10.1172/jci82799	journal	August 2015
Mechanisms of protein-folding diseases at a glance Valastyan, J. S.; Lindquist, S. Disease Models & Mechanisms, Vol. 7, Issue 1 https://doi.org/10.1242/dmm.013474	journal	January 2014
How Protein Stability and New Functions Trade Off Tokuriki, Nobuhiko; Stricher, Francois; Serrano, Luis PLoS Computational Biology, Vol. 4, Issue 2 https://doi.org/10.1371/journal.pcbi.1000002	journal	February 2008
ECOD: An Evolutionary Classification of Protein Domains Cheng, Hua; Schaeffer, R. Dustin; Liao, Yuxing PLoS Computational Biology, Vol. 10, Issue 12 https://doi.org/10.1371/journal.pcbi.1003926	journal	December 2014
Biophysical Characterization of the Olfactomedin Domain of Myocilin, an Extracellular Matrix Protein Implicated in Inherited Forms of Glaucoma Orwig, Susan D.; Lieberman, Raquel L. PLoS ONE, Vol. 6, Issue 1 https://doi.org/10.1371/journal.pone.0016347	journal	January 2011
Molecular Details of Olfactomedin Domains Provide Pathway to Structure-Function Studies Hill, Shannon E.; Donegan, Rebecca K.; Nguyen, Elaine PLOS ONE, Vol. 10, Issue 6 https://doi.org/10.1371/journal.pone.0130888	journal	June 2015
PHENIX: a comprehensive Python-based system for macromolecular structure solution. Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.45787	text	January 2010
Olfactomedin proteins: central players in development and disease Anholt, Robert R. H. Frontiers in Cell and Developmental Biology, Vol. 2 https://doi.org/10.3389/fcell.2014.00006	journal	January 2014

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extracellular matrix protein
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Stable calcium-free myocilin olfactomedin domain variants reveal challenges in differentiating between benign and glaucoma-causing mutations

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