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

Hill, Shannon E.; Donegan, Rebecca K.; Nguyen, Elaine; Desai, Tanay M.; Lieberman, Raquel L.; Anderson, Michael G.

doi:10.1371/journal.pone.0130888

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

Journal Article · Mon Jun 29 00:00:00 EDT 2015 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0130888· OSTI ID:1245865

Hill, Shannon E. ^[1]; Donegan, Rebecca K. ^[1]; Nguyen, Elaine ^[1]; Desai, Tanay M. ^[1]; Lieberman, Raquel L. ^[1]; Anderson, Michael G. ^[2]

Georgia Inst. of Technology, Atlanta, GA (United States)
Univ. of Iowa, Iowa City, IA (United States)

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.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health

Grant/Contract Number:: R01EY021205; W-31-109-Eng-38

OSTI ID:: 1245865

Journal Information:: PLoS ONE, Vol. 10, Issue 6; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

Citation Metrics:

Cited by: 15 works

Citation information provided by
Web of Science

References (55)

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
Electrostatics of nanosystems: Application to microtubules and the ribosome Baker, N. A.; Sept, D.; Joseph, S. Proceedings of the National Academy of Sciences, Vol. 98, Issue 18, p. 10037-10041 https://doi.org/10.1073/pnas.181342398	journal	August 2001
Genetic dissection of myocilin glaucoma Gong, G. Human Molecular Genetics, Vol. 13, Issue 90001 https://doi.org/10.1093/hmg/ddh074	journal	January 2004
Structural Basis of Latrophilin-FLRT Interaction Jackson, Verity A.; del Toro, Daniel; Carrasquero, Maria Structure, Vol. 23, Issue 4 https://doi.org/10.1016/j.str.2015.01.013	journal	April 2015
DISPLAR: an accurate method for predicting DNA-binding sites on protein surfaces Tjong, Harianto; Zhou, Huan-Xiang Nucleic Acids Research, Vol. 35, Issue 5 https://doi.org/10.1093/nar/gkm008	journal	February 2007
Noelin-1 is a secreted glycoprotein involved in generation of the neural crest Barembaum, Meyer; Moreno, Tanya A.; LaBonne, Carole Nature Cell Biology, Vol. 2, Issue 4 https://doi.org/10.1038/35008643	journal	March 2000
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
Olfactomedin Domain-Containing Proteins: Possible Mechanisms of Action and Functions in Normal Development and Pathology Tomarev, Stanislav I.; Nakaya, Naoki Molecular Neurobiology, Vol. 40, Issue 2 https://doi.org/10.1007/s12035-009-8076-x	journal	June 2009
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
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
Olfactomedin 4 Inhibits Cathepsin C-Mediated Protease Activities, Thereby Modulating Neutrophil Killing of Staphylococcus aureus and Escherichia coli in Mice Liu, Wenli; Yan, Ming; Liu, Yueqin The Journal of Immunology, Vol. 189, Issue 5 https://doi.org/10.4049/jimmunol.1103179	journal	July 2012
Characterization of extracellular circulating microRNA Turchinovich, Andrey; Weiz, Ludmila; Langheinz, Anne Nucleic Acids Research, Vol. 39, Issue 16 https://doi.org/10.1093/nar/gkr254	journal	May 2011
Glaucoma-associated myocilin: A better understanding but much more to learn Resch, Zachary T.; Fautsch, Michael P. Experimental Eye Research, Vol. 88, Issue 4 https://doi.org/10.1016/j.exer.2008.08.011	journal	April 2009
Zebrafish Olfactomedin 1 Regulates Retinal Axon Elongation In Vivo and Is a Modulator of Wnt Signaling Pathway Nakaya, N.; Lee, H. -S.; Takada, Y. Journal of Neuroscience, Vol. 28, Issue 31 https://doi.org/10.1523/JNEUROSCI.0617-08.2008	journal	July 2008
Pancortin-2 Interacts with WAVE1 and Bcl-xL in a Mitochondria-Associated Protein Complex That Mediates Ischemic Neuronal Death Cheng, A.; Arumugam, T. V.; Liu, D. Journal of Neuroscience, Vol. 27, Issue 7 https://doi.org/10.1523/JNEUROSCI.5154-06.2007	journal	February 2007
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
Pancortins interact with amyloid precursor protein and modulate cortical cell migration Rice, H. C.; Townsend, M.; Bai, J. Development, Vol. 139, Issue 21 https://doi.org/10.1242/dev.082909	journal	September 2012
A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to ADHD and predicts effectiveness of stimulant medication Arcos-Burgos, M.; Jain, M.; Acosta, M. T. Molecular Psychiatry, Vol. 15, Issue 11 https://doi.org/10.1038/mp.2010.6	journal	February 2010
Increasing the hydrophobic interaction between terminal W-motifs enhances the stability of Salmonella typhimurium sialidase. A general strategy for the stabilization of β-propeller protein fold Witarto, Arief Budi; Sode, Koji Protein Engineering, Design and Selection, Vol. 14, Issue 11 https://doi.org/10.1093/protein/14.11.891	journal	November 2001
The many blades of the β-propeller proteins: conserved but versatile Chen, Cammy K. -M.; Chan, Nei-Li; Wang, Andrew H. -J. Trends in Biochemical Sciences, Vol. 36, Issue 10 https://doi.org/10.1016/j.tibs.2011.07.004	journal	October 2011
ESPript/ENDscript: extracting and rendering sequence and 3D information from atomic structures of proteins Gouet, P. Nucleic Acids Research, Vol. 31, Issue 13 https://doi.org/10.1093/nar/gkg556	journal	July 2003
Hormonal regulation of endometrial olfactomedin expression and its suppressive effect on spheroid attachment onto endometrial epithelial cells Kodithuwakku, S. P.; Ng, P. -Y.; Liu, Y. Human Reproduction, Vol. 26, Issue 1 https://doi.org/10.1093/humrep/deq298	journal	November 2010
Increased expression of olfactomedin-1 and myocilin in podocytes during puromycin aminonucleoside nephrosis Bohr, D. C.; Koch, M.; Kritzenberger, M. Nephrology Dialysis Transplantation, Vol. 26, Issue 1 https://doi.org/10.1093/ndt/gfq366	journal	June 2010
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
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
Ligands for Glaucoma-Associated Myocilin Discovered by a Generic Binding Assay Orwig, Susan D.; Chi, Pamela V.; Du, Yuhong ACS Chemical Biology, Vol. 9, Issue 2 https://doi.org/10.1021/cb4007776	journal	November 2013
Long-Term Maintenance of Na+ Channels at Nodes of Ranvier Depends on Glial Contact Mediated by Gliomedin and NrCAM Amor, V.; Feinberg, K.; Eshed-Eisenbach, Y. Journal of Neuroscience, Vol. 34, Issue 15 https://doi.org/10.1523/JNEUROSCI.4752-13.2014	journal	April 2014
Biology of purinergic signalling: Its ancient evolutionary roots, its omnipresence and its multiple functional significance: Prospects & Overviews Verkhratsky, Alexei; Burnstock, Geoffrey BioEssays, Vol. 36, Issue 7 https://doi.org/10.1002/bies.201400024	journal	April 2014
MicroRNAs Shape the Neuronal Landscape McNeill, Elizabeth; Van Vactor, David Neuron, Vol. 75, Issue 3 https://doi.org/10.1016/j.neuron.2012.07.005	journal	August 2012
PIC: Protein Interactions Calculator Tina, K. G.; Bhadra, R.; Srinivasan, N. Nucleic Acids Research, Vol. 35, Issue Web Server https://doi.org/10.1093/nar/gkm423	journal	May 2007
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 beta bulge: a common small unit of nonrepetitive protein structure. Richardson, J. S.; Getzoff, E. D.; Richardson, D. C. Proceedings of the National Academy of Sciences, Vol. 75, Issue 6 https://doi.org/10.1073/pnas.75.6.2574	journal	June 1978
Docking Server for the Identification of Heparin Binding Sites on Proteins Mottarella, Scott E.; Beglov, Dmitri; Beglova, Natalia Journal of Chemical Information and Modeling, Vol. 54, Issue 7 https://doi.org/10.1021/ci500115j	journal	July 2014
Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features Kabsch, Wolfgang; Sander, Christian Biopolymers, Vol. 22, Issue 12 https://doi.org/10.1002/bip.360221211	journal	December 1983
PROMALS3D: a tool for multiple protein sequence and structure alignments Pei, Jimin; Kim, Bong-Hyun; Grishin, Nick V. Nucleic Acids Research, Vol. 36, Issue 7 https://doi.org/10.1093/nar/gkn072	journal	February 2008
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
SWISS-MODEL and the Swiss-Pdb Viewer: An environment for comparative protein modeling Guex, Nicolas; Peitsch, Manuel C. Electrophoresis, Vol. 18, Issue 15, p. 2714-2723 https://doi.org/10.1002/elps.1150181505	journal	January 1997
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
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
Myocilin allele-specific glaucoma phenotype database Hewitt, Alex W.; Mackey, David A.; Craig, Jamie E. Human Mutation, Vol. 29, Issue 2 https://doi.org/10.1002/humu.20634	journal	February 2008
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
A genome-wide association meta-analysis identifies new childhood obesity loci Nature Genetics, Vol. 44, Issue 5, p. 526-531 https://doi.org/10.1038/ng.2247	journal	April 2012
Olfactomedin-4 is a glycoprotein secreted into mucus in active IBD Gersemann, Michael; Becker, Svetlana; Nuding, Sabine Journal of Crohn's and Colitis, Vol. 6, Issue 4 https://doi.org/10.1016/j.crohns.2011.09.013	journal	May 2012
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
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
Deletion of olfactomedin 2 induces changes in the AMPA receptor complex and impairs visual, olfactory, and motor functions in mice Sultana, Afia; Nakaya, Naoki; Dong, Lijin Experimental Neurology, Vol. 261 https://doi.org/10.1016/j.expneurol.2014.09.002	journal	November 2014
Olfactomedin-1 activity identifies a cell invasion checkpoint during epithelial-mesenchymal transition in the chick embryonic heart Lencinas, A.; Chhun, D. C.; Dan, K. P. Disease Models & Mechanisms, Vol. 6, Issue 3 https://doi.org/10.1242/dmm.010595	journal	December 2012
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
Novel Sequences Propel Familiar Folds Jawad, Zahra; Paoli, Massimo Structure, Vol. 10, Issue 4 https://doi.org/10.1016/s0969-2126(02)00750-5	journal	April 2002
Characterization and differential expression of a human gene family of olfactomedin-related proteins Kulkarni, Nalini H.; Karavanich, Christa A.; Atchley, William R. Genetical Research, Vol. 76, Issue 1 https://doi.org/10.1017/s0016672300004584	journal	August 2000
Fibronectin Type III-like Domains of Neurofascin-186 Protein Mediate Gliomedin Binding and Its Clustering at the Developing Nodes of Ranvier Labasque, Marilyne; Devaux, Jérôme J.; Lévêque, Christian Journal of Biological Chemistry, Vol. 286, Issue 49 https://doi.org/10.1074/jbc.m111.266353	journal	October 2011
Olfactomedin 1 Interacts with the Nogo A Receptor Complex to Regulate Axon Growth Nakaya, Naoki; Sultana, Afia; Lee, Hee-Sheung Journal of Biological Chemistry, Vol. 287, Issue 44 https://doi.org/10.1074/jbc.m112.389916	journal	August 2012
Cleavage and Oligomerization of Gliomedin, a Transmembrane Collagen Required for Node of Ranvier Formation Maertens, Barbara; Hopkins, Delana; Franzke, Claus-Werner Journal of Biological Chemistry, Vol. 282, Issue 14 https://doi.org/10.1074/jbc.m611339200	journal	February 2007
Targeted Disruption of the Myocilin Gene (Myoc) Suggests that Human Glaucoma-Causing Mutations Are Gain of Function Kim, B. S.; Savinova, O. V.; Reedy, M. V. Molecular and Cellular Biology, Vol. 21, Issue 22 https://doi.org/10.1128/mcb.21.22.7707-7713.2001	journal	November 2001
A genome-wide association meta-analysis identifies new childhood obesity loci Bradfield JP, -; Taal HR, -; Timpson NJ, - Obesity and metabolism, Vol. 9, Issue 1 https://doi.org/10.14341/2071-8713-5058	journal	March 2012

Cited By (5)

Binding of a glaucoma-associated myocilin variant to the αB-crystallin chaperone impedes protein clearance in trabecular meshwork cells Lynch, Jeffrey M.; Li, Bing; Katoli, Parvaneh Journal of Biological Chemistry, Vol. 293, Issue 52 https://doi.org/10.1074/jbc.ra118.004325	journal	November 2018
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. Journal of Biological Chemistry, Vol. 294, Issue 34 https://doi.org/10.1074/jbc.ra119.009419	journal	July 2019
Calcium-ligand variants of the myocilin olfactomedin propeller selected from invertebrate phyla reveal cross-talk with N-terminal blade and surface helices Hill, Shannon E.; Cho, Hayeon; Raut, Priyam Acta Crystallographica Section D Structural Biology, Vol. 75, Issue 9 https://doi.org/10.1107/s205979831901074x	journal	August 2019
Design and structural characterisation of olfactomedin-1 variants as tools for functional studies Pronker, Matti F.; van den Hoek, Hugo; Janssen, Bert J. C. BMC Molecular and Cell Biology, Vol. 20, Issue 1 https://doi.org/10.1186/s12860-019-0232-1	journal	November 2019
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

Similar Records

Differential Misfolding Properties of Glaucoma-Associated Olfactomedin Domains from Humans and Mice

Journal Article · Mon Feb 25 00:00:00 EST 2019 · Biochemistry · OSTI ID:1245865

Patterson-Orazem, Athéna C.; Hill, Shannon E.; Wang, Yiming; +3 more

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 · OSTI ID:1245865

Hill, Shannon E.; Kwon, Michelle S.; Martin, Mackenzie D.; +5 more

Trifunctional High-Throughput Screen Identifies Promising Scaffold To Inhibit Grp94 and Treat Myocilin-Associated Glaucoma

Journal Article · Mon Feb 05 00:00:00 EST 2018 · ACS Chemical Biology · OSTI ID:1245865

Huard, Dustin J. E.; Crowley, Vincent M.; Du, Yuhong; +9 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Protein domains
Crystal structure
Heparin
Binding analysis
Molecular structure
Glaucoma
Thermal stability
Disulfide bonds

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

Citation Formats

References (55)

Cited By (5)

Similar Records

Related Subjects